EPM September 2014

epm www.epmmagazine.com

IN THIS ISSUE: CPhI Preview Solid Dosage Coating Bioavailability Plus – the latest news and opinion

SEPTEMBER 2014

Volume 14 | Issue 06

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epm www.epmmagazine.com

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

Contents 6

NEWS

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NEWS PROFILE

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NEWS ANALYSIS

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OPINION This issue Bosch and Biotec contribute to the debate plus we kick-start our new It’s Good to Talk feature

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CPhI Highlights from this key event

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SOLID DOSAGE COATING Hermes and Colorcon offer insight

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MIXING & BLENDING

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WEIGHING

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

editorial group editor lu rahman, lu.rahman@rapidnews.com

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contributing editor aleksandra jones, ola@rapidnews.com

MANUFACTURING PROCESSES Schott and Vanrx in the spotlight

publishers mark blezard, duncan wood

production

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art samantha hamlyn

CLEANROOMS Expertise from Cherwell Laboratories

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

BIOAVAILABILITY Jon Sutch, Patheon offers solutions for poorly soluble drugs

subscriptions subscriptions@rapidnews.com qualifying readers

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DIGITAL PHARMA Veeva explains the benefits of the cloud to the pharma sector

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outside qualifying criteria UK - £80, ROW - £115 please subscribe online at www.epmmagazine.com

HIGH PROTEIN ANALYSIS

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Address changes should be emailed to subscriptions@rapidnews.com.

European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd.

REGULATORY AFFAIRS EPM’s regular column from the EPC

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CHEMICAL REACTION This month, Ergomed in focus

European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals.

Volume 14 Issue 6 © September 2014.

While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

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Merck Millipore is a division of

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4/15/14 4:23 PM

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COMMENT

It’s not about the money, money, money...

The cost of drugs is constant headline fodder.

The topic creates immediate response and controversy – why should an individual be denied treatment due to the cost of a medicine, especially when their life may depend upon it?

However, behind the headlines the issue isn’t so straightforward.

It was interesting to recently read the views of a cardio expert. He notes that while there is a growing range of drugs on the market, shown to offer life-prolonging benefits, these are not always prescribed on cost grounds. His suggestion to help such drugs become more widely available, is that doctors need to go back to prescribing tried and tested drugs that have been shown to offer known benefits and of which they can be confident. This will then help fund the drugs that may be more expensive.

He notes a trend where doctors have moved away from these type of drugs to newer, more expensive ones, due to a belief that drug companies have been misleading the medical profession over the benefits of these products and that in order for them to get back to making the right choices, the evidence surrounding the efficacy of certain products needs to be clearer.

This is where the subject becomes cloudier and more controversial. In order to carry out randomised controlled trials, drug company sponsorship is often required to pull together results from thousands of patients across several continents. When the headlines continue to tell us the use of certain drugs is influenced by a pharmaceutical company’s desire to make money, and when the public gets to know particular companies are involved in the financing of trials, indignation kicks in and we have the perfect conditions for attentiongrabbing headlines.

Of course, the situation isn’t so clear cut.

Pharmaceutical companies need to make money and the cost of a drug is like anything else – relative to demand and the marketplace.

One way of bridging the gap, says the cardio expert, is for the medical profession to insist on receiving transparent data of the drug development process. We need to stop looking at the person and the profit if we are to tackle this issue. While we continue to hold up profit as an evil, and one which holds back the more widespread use of other drugs, we aren’t helping pharmaceutical companies and we may run the risk of data of negative results being withheld in order to maintain profits.

What we also run the risk of, is holding back innovation and development. Without funding, without profit, how are we to finance future excellence and attract the individuals that have the skills and knowledge to help us reach new pharmaceutical heights? It’s clear that innovation is paramount to this sector, which is why headlines highlighting the cost of drugs become all the more problematic to read.

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Lu Rahman

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NEWS

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ccording to a report from Euler Hermes, despite being the UK’s leading exporter and employing 70,000 people, the pharmaceutical industry is failing to contribute to the country’s economic growth. Pharmaceutical production is contributing nothing to the increase in GDP – instead recording a 4% contraction between 2009 and 2013. And all of this at a time when Britain is struggling against Ireland’s attractive low corporate tax rates.

The full Economic Outlook report highlights that the pharmaceuticals sector, which includes AstraZeneca and GSK, two labs amongst the 10 largest worldwide, is the leader in exports (7% of total exports) for the UK. Its national production stands at USD 24 billion. The sector is known for its innovation, as it boasts 25% of R&D expenditures (GBP 4.2 billion in 2012) and employs 70,000 persons (0.2% of the total

Irish pharma beats UK in contribution to GDP labour force), of which over one third are in highly skilled positions.

The pharmaceutical sector is one of the eleven strategic sectors for the government, along with aeronautics, automobile, nuclear, and financial services sectors.

However, this does not necessarily mean, says the report, that the sector contributed to the economic recovery.

In 2013, GDP grew at its highest rate in the last 6 years (+1.7%) and should display the strongest performance in the region moving forward: +2.6% in 2014

and +2.5% in 2015. However, pharmaceutical production didn’t contribute at all – it contracted by an average of -4% between 2009 and 2013. Productivity losses have been accelerating since 2007, and exports have quickly lost momentum. Due to this, the trade surplus, which hit a peak of GBP 7 billion in 2009 and 2010, has hit a low of GBP 2.8 billion in 2013. As a result, says Euler, the true catalyst of the British revival since 2013 has been services (notably financial services), which account for around 80% of GDP. According to Euler, the UK may well be a victim of the Irish fiscal illusion.

Contrarily to its neighbours, Irish pharmaceuticals have registered an average annual growth of +9% over 2009-13. This is a result of the fiscal attractiveness when compared with countries across the channel.

While corporate tax rates are at 40% in the US and 23% on average in the EU, UK rates will drop to 20% in April 2015, the lowest within the G-20. It is therefore easy to imagine Pfizer’s potential gains in moving its headquarters from the US to the UK had its takeover of rival AstraZeneca materialized. However, with rates at 12.5%, Ireland pushes the British economy to its limits. But this also increases the dependence of the country’s economy on the sector: pharmaceuticals represent 30% of total Irish exports and 27% of GDP. Therefore vulnerability is high as shown in 2013 when GDP fell by 1.2% year over year (y/y) due to the expiration of multiple patents while GNP increased by 2.6% y/y.

European pharma to emerge as consolidators as US targets release key clinical data European pharmaceutical firms looking to add to their portfolios could take advantage of a slew of US assets releasing late-stage clinical data and a calmer crossborder M&A market due to a possible clampdown on US tax inversion deals, Mergermarket Group intelligence said.

enhance existing pipelines, the bankers and analysts said.

Pharmacyclics have been named as targets within this range.

Roche and Sanofi which are both on the hunt for acquisitions, could also be sounding out targets across the Atlantic to add advanced technologies and new orphan drug development science.

Jazz Pharmaceuticals and Salix Pharmaceuticals, which are both UKheadquartered, also fall within this deal range, but European pharma would have to compete with US bidders willing to pay a tax inversion premium.

UK-based AstraZeneca and GlaxoSmithKline which have spent the first half of the year reorganising their portfolios, could now look to the US in an effort to replenish and

US firms in the USD 5-10bn size range would be affordable and provide European bidders with long-term revenues. InterMune, BioMarin, Incyte Corporation and

AstraZeneca and GSK, which have both undertaken strategies that have led them to focus on respiratory disorders, can better reap revenue if

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they have a presence across the gamut of respiratory indications, it has been suggested.

An acquisition of US-based InterMune, which has filed pirfenidone for idiopathic pulmonary fibrosis (IPF) for approval with the US FDA and is awaiting a response in 4Q14, would be a good fit for either AstraZeneca or GSK, it has been said. GSK declined to comment.

AstraZeneca did not return a request for comment.

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The opportunity to help an already successful company develop its business into exciting global markets and also to take the lead in developing the teams who will ultimately deliver results in these new territories and leave a lasting legacy for the business.

What areas do you plan to focus on?

Elfab plans to grow significantly over the next few years, further penetrating its existing markets, as well as developing sales in new markets. Geographical growth areas for the company include the Middle East, Africa and Russia.

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Elfab is the only manufacturer to offer a complete line of pressure relief solutions benefiting from some of the best technical characteristics and non-invasive detection systems on the market. Using its exceptional in-house process capabilities Elfab manufactures solutions in line with its customers’ increasingly stringent health, safety and environmental requirements.

Where do you see the business in five years time?

Within five years the expectation is that the business will have doubled in size and that over 30% of the businesses sales will be driven by new territory development, predominantly in the Middle East, Africa and Russia.

With regards to product development, Elfab will be exploring new technology to keep it at the forefront of innovation while continuing to offer the most technical advanced rupture discs on the market. Further advancements in burst detection are also on the horizon, including the recent interest in wireless systems.

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NEWS PROFILE

Inspired choice Named as one of the top 100 most inspiring people in life sciences is a some achievement. As PharmaVOICE 100 lists Dr Chitra Lele, Sciformix Corporation, as one such individual, we look at how her work has transformed the sector and led to this award

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r Chitra Lele, chief scientific officer at Sciformix Corporation, has been active in the pharmaceutical industry, and in epidemiological research, for over 20 years. Over the course of her career she has made some significant contributions to the life science sector, particularly in the offshoring of biometrics and medical writing. Her extensive work has created a shift in how the industry sources design, analysis, and the reporting of clinical trials.

This has led to a permanent shift in the operating model and the establishment of new frontiers.

Lele has helped expand the global reach of Sciformix’s services by going to where the talent pool is based, to provide the best quality support to its clients. She has evolved new, niche solutions and services in safety signal detection and post-approval based on emerging trends. She has also been instrumental in driving the positioning of the company as an scientific process outsourcing (SPO) in the industry, through contribution of thought leadership articles and presentations in emerging areas in a broad range of life science publications – it is this expertise and knowledge of the sector which has fuelled her success.

“The industry is currently in a very dynamic state, with challenges

Aiming high: One of Lele’s real aims is to assist in implementing initiatives that fulfil the needs of the industry

on all fronts, pushing it to break conventional barriers and move towards new horizons,” comments Lele. “In order for life science and pharmaceutical companies to best progress, they should understand these changes and see how they can work to their advantage. Making the most of a more connected, global and accessible community can open up a whole new range of opportunities to those with the right tools and processes.”

Lele has played a crucial role from the early stages of her career in developing and rolling out several offshore pharmacovigilance and biometrics operations in India.

She has also developed an outsourcing strategy for clinical data management and strategising and implementing a new model for partnering with Contract Research Organisations (CROs).

The result of these initiatives was increased capacity building in the CRO industry, leading to largescale offshoring of biometrics and medical writing in a functional service provider model from costeffective locations, with several pharmaceutical companies taking advantage of the talent pool. By properly managing outsourcing and ensuring the required standards are met, the process dramatically improves how work is managed in today’s expanding market.

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The industry is currently in a very dynamic state, with challenges on all fronts, pushing it to break conventional barriers and move towards new horizons.

On embracing new frontiers, and the challenges these present to the life sciences, particularly those in the digital realm, Lele is determined to curate and implement technologybased solutions to keep the industry moving forward.

“Electronic health records, social media and ‘Big Data’ are forcing a revolution that the industry has to embrace,” Lele explains. “With new operating and partnership models emerging across product development and lifecycle maintenance, new cross functional and technology-based innovative offerings are sorely required.

One of my real aims is to assist in implementing initiatives that fulfil this need of the industry.”

As a founding member of regional industry associations, Lele has also been responsible for promoting clinical research training. She has played an integral role in helping bring through the next generation of scientists, by working as a visiting faculty member in Indian universities, developing and

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teaching new masters level courses.

Support for those who do not receive adequate healthcare due to their financial status is a key concern for Lele. She hopes safer medicines become more available to a larger section of the population.

“Everyone is aware of the skyrocketing costs of specialised healthcare that prevents those in need from receiving treatment,” she explains. “I support an excellent public-professional partnership aimed at providing affordable or subsidised quality healthcare to the less fortunate sections of society.”

Lele has made real strides in improving how clinical trials are planned, executed and reported globally, opening up new frontiers for clinical trial data management and reporting as well as pharmacovigilance and drug safety.

This has provided opportunities for companies looking to improve efficiencies across the product lifecycle in order to make better and safer medicines available to a larger number of patients.

NEWS PROFILE

Your industry needs you EPM and Astec IT Solutions have partnered together to create a survey to understand the issues facing the pharmaceutical sector. The results will form a white paper highlighting the key topics and challenges pharma business faces. But we need your help to do it...

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PM has partnered with Astec IT Solutions for a survey looking at operational excellence in the pharmaceutical sector. The results will create an overview of pharmaceutical manufacturing that will offer insight in to the key issues affecting the industry and help us gain an understanding of the challenges you face and ways to overcome them.

By now you should have seen the email survey – please take a few minutes to complete it to help create a snapshot into the sector at the moment. As a manufacturer, your opinion is valued and it provides the perfect way for us to understand the drivers and obstacles you face on a daily basis.

Key topics covered will include the type of products you provide, the effects of product recalls on your business and the process you go through when this occurs.

We’re interested in the key factors that affect your business – is it compliance, waste or costs perhaps? How much of a problem are bottlenecks to your company?

We would also like to understand the level to which your business is digitised and where you see innovation and manufacturing trends coming from in the near future.

Lu Rahman, EPM group editor, said: “We are looking forward to the findings of this project.

Understanding the issues that the pharmaceutical manufacturer faces will give us a valuable insight

into the industry. EPM is the voice of the European pharmaceutical industry – it is your publication. As a magazine we are always looking to provide content that delivers the most impact and has the most relevance to the reader. This survey should help us fine tune our offering and we hope that as many of you as possible are able to help us do this.”

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Understanding the issues that the pharmaceutical manufacturer faces will give us a valuable insight into the industry

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“Astec IT Solutions is an ideal partner to work with on this study and the company will be taking the results to create a white paper that will offer the sector key information to help us understand the challenges and business issues it faces on a regular basis.”

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NEWS ANALYSIS

Point of view Aleksandra Jones outlines the importance of plastics in the production of ready-to-fill syringes

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or many years glass has been treated as the ‘gold standard’ in packaging of most of liquid medications and syringes.

Its qualities are undeniable: it rarely reacts with the substances it holds and it doesn’t allow for fluids, vapours and oxygen to pass through. It is also transparent, which allows a quick inspection of the contents, and is easy to mould into different shapes, dependent on the purpose of the particular item.

Nevertheless, many of us are also familiar with plastic syringes, which have been around for some time.

They have mostly been produced from polyethylene or polypropylene, which means they can be made a lot cheaper than their glass equivalents. However, they are not designed to hold liquid medication for longer and can only be filled right before the injection takes place. This is in contrast to glass, which can be used to store liquids for several years.

Alternative to glass Glass, with its many advantages, is however prone to breakage, which is one of the reasons why finding a suitable alternative has been vital for both the pharmaceutical and the medical industries. Syringe producers started using a plastic called cyclic olefin copolymer (COC)/cyclic olefin copolymer (COP) several years ago and it turned out to be a much more viable solution than using cheaper polyethylene and polypropylene.

COC/COP is transparent, which means that the contents can be instantly inspected for clouding or other changes. It doesn’t break as easily as glass, making it a lot more durable; this stops unnecessary wastage of expensive medications.

The most important property, however, is the fact that COC/COP acts as a relatively good barrier against water vapour and oxygen and provides adequate protection for the pharmaceutical it holds.

Many drugs available on the market are expensive to produce and any wastage incurs high costs for the company; this means not only breakages, but also exposing the medication to the influence of external conditions. COC/COP syringes, thanks to their high quality, are often used as packaging for injectable biotechnologically derived drugs, which are both expensive and highly susceptible to external conditions. Hyaluronic acid, used in orthopaedics, cosmetic surgery and other treatments, as well as opthalmics, is an example of product that requires high-quality packaging, and is filled into COC/ COP syringes.

No interim cleaning The production of COC/COP syringes requires cleanroom conditions, and is usually done without human involvement, in a fully automated process. That means that syringes produced in this way don’t require interim cleaning stages, as it is in the case of glass syringe production, which involves washing the products with pharmaceutical water and eliminating glass dust. COC/ COP syringes are produced using high-precision injection moulding, with cyclic olefin polymer granules being poured into the injection moulding machine. This allows for tight tolerances and accurate geometries of the ready product, which means that less medication residue remains in the syringe after the injection — it is an important argument in the case of expensive pharmaceuticals, where any quantity of wasted product incurs large costs.

Of course syringes are used for a variety of drugs and there isn’t one type or material that will suit all applications perfectly. Cost is very often the deciding factor in decision-making processes of healthcare providers, provided it

doesn’t have implications on the safety of the patients. Increasingly the option of ready-to-fill syringes wins, as it becomes more common for patients to dispense their medications themselves or have administered at home by a health professional or another qualified person. This saves both the personnel time and costs, both of which are limited in modern healthcare systems.

Taking all this into consideration, cooperation of syringe manufacturers and pharmaceutical companies is extremely important.

Collaboration at the very early stages of drug development can save a lot of time and money spent on researching the best syringe solution for a particular medication.

Importance of choice It is vital that options exist for the pharmaceutical industry, especially where syringes are concerned. While COC/COP might be the best solution for innovative biotechnologically developed drugs, it is still more expensive than glass and does not possess exactly the same properties — glass is more gas/vapour permeable and inert and it will continue to be a viable option for many pharmaceutical manufacturers. In time, however, COC/COP syringes will certainly continue to develop and will be used increasingly for expensive applications requiring less wastage.

In the case of some medications there are also legal requirements that need to be followed. The environment in which medication is administered is also an important factor in choosing the right syringe for the job: cheaper syringes made of polyethylene or polypropylene can be used in hospitals, medical centres or clinics, but for selfmedication ready-to-fill syringes might be the best option.

This article used materials provided by Gerresheimer (www. gerresheimer.com) and Schott (www.schott.com).

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Going for gold: For many years glass has been treated as the ‘gold standard’ in packaging of most of liquid medications and syringes

NEWS PROFILE Added value The addition of microcalorimetry to Malvern Instruments portfolio extends its offering for biopharmaceuticals

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n July this year Malvern Instruments completed the acquisition of MicroCal from GE Healthcare Life Sciences. MicroCal has a 30-year track record of developing and supplying easy-touse microcalorimeters, instruments that are used to study proteins and other biomolecules in drug discovery and development. At the same time, Malvern announced that it had acquired the Archimedes particle characterization system from Affinity Biosensors. Both of these developments mark a further step in the extension of Malvern’s analytical tools for life science applications.

Meeting pharma challenges The pharmaceutical industry currently faces multiple challenges.

In the traditional small molecule area, lengthening times to market, coupled with intense generic activity, have prompted a shift in focus towards manufacturing efficiency.

The implementation of a knowledgeled QbD approach that reduces risk across the product lifecycle has also proven an important driver for change. More fundamentally however, the (at times faltering) drug pipeline is now being filled with biopharmaceuticals, a trend that brings with it a new range of challenges.

A trusted supplier Malvern is a long-established and well-known supplier of analytical instrumentation to the pharmaceutical and other industries. It provides tools that deliver essential information for applications ranging from the characterisation of proteins and polymers in solution, particle and nanoparticle suspensions and emulsions, through to sprays and aerosols, industrial bulk powders and high concentration slurries. A driving force behind all of Malvern’s

Crowd pleaser: The MicroCal team pictured at the Northampton Massachussetts facility which will become a centre of excellence for microcalorimetry.

developments and acquisitions is always to deliver to its customers the information they need to help accelerate research and product development, enhance and maintain product quality and optimize process efficiency.

Within the pharmaceutical industry Malvern is focused on providing well designed, innovative analytical instruments, which follow the QbD (Quality by Design) ethos, in the fields of drug discovery, chemical and formulation development and pharmaceutical manufacturing. As biotherapeutics has increasingly become the target of significant investment and rapid growth worldwide, Malvern has moved to ensure that it takes a leading role in providing appropriate solutions to meet the highly demanding analytical needs of the sector. This is being achieved in a number of ways, through in house development and via technology acquisition.

In 2012 Malvern established the Bioscience Development Initiative, through which it is driving a program of high-level partnering for technology development, collaborating with biopharmaceutical companies and industry leaders, working with academia and small

start-ups to access leadingedge technology and with more established companies to license it in. This enables the Malvern teams to test concepts and engineer prototypes to provide industry partners with early access to the measurement solutions of tomorrow, to refine the offering with their expert input, and deliver the tools that meet the specific and rapidly evolving analytical needs of the sector.

The acquisition of MicroCal further strengthens Malvern’s analytical solutions for customers in core pharmaceutical and biopharmaceutical markets, immediately providing customers with a range of proven microcalorimetry products for drug discovery and development applications. While the purchase of the Archimedes product is unrelated to the MicroCal acquisition, it again strengthens the portfolio for biotherapeutic development.

Solutions and support to life science “Microcalorimetry is now an essential tool that is used at almost every stage of the drug discovery, development and

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formulation process,” said Paul Walker, managing director of Malvern Instruments. “MicroCal is an established technology leader in the field and MicroCal products are an excellent fit with Malvern’s existing portfolio of measurement solutions for the pharmaceutical and biopharmaceutical industries. Their ability to deliver information about drug binding and protein stability is entirely complementary to Malvern’s current products and to those in development. This addition to our business has an immediate impact on Malvern’s ability to provide a complete range of instrumentation solutions and support across life science research and development.”

Microcalorimetry is a universal technique that has particular application in drug discovery and development involving proteins and other biomolecules, and is used at almost every stage of the process.

Consequently MicroCal differential scanning calorimeters (DSC) and isothermal titration calorimeters (ITC) are used in areas from basic research to the discovery and development of small molecules, biotherapeutics and vaccines.

A current emphasis on structurebased drug design and rapid advances in biopharmaceutical development are driving an increase in the use of microcalorimetry as a standard technique in pharmaceutical research. Its use provides scientists with detailed information across several stages of the drug discovery process, reducing the potential for late-stage drug candidate failures.

Further investment will see Malvern advancing MicroCal’s Northampton, Massachussetts facility with plans to develop it as a Center of Excellence for Microcalorimetry.

OPINION

The secret’s out . . .

Q& A

Earlier this year, Martin Lamb joined what he describes as ‘the best kept secret in the industry’.

With a few months under his belt as commercial director, Lamb explains his role and future plans for future success at Biotec Services

EPM: What is your role at Biotec Services International and what does it involve?

ML: I’m responsible for the management of business development, marketing and project management teams. In other companies business development/ marketing sits separately from project management but both roles are customer-facing. Business development works with customers to agree project scope; project management works with the customer to deliver against that scope and marketing collects customer feedback from both to formulate a business strategy to more closely match the clients’ requirements.

During my time in clinical supplies, budget management became a key customer requirement as clinical development costs continue to grow. Closer working between business development and project management means that we can monitor spend against our initial plans, alert clients to potential overspends and work co-operatively with them to get it back on track.

EPM: What are your plans for the company going forwards?

ML: One of my first tasks on joining Biotec was to get a feel for how our clients view our service. Feedback was excellent – 97% of our current clients would recommend us.

However, it is fair to say that we remain unknown to a large number of companies in our market. My first task will be to address this by raising our profile and increasing awareness of our services.

Biotec offers flexibility and fast turnaround times without sacrificing quality, key requirements in today’s increasingly just-in-time approach

to clinical supply packaging and distribution. We have invested heavily in our cold-chain capacity, and in our online reporting technologies. I plan to work with our customers and the Biotec team to continue to improve customers’ access to the information they need.

Finally, I will be looking at our global reach. We have increased this through a network of partner depots around the world. I am evaluating this model at present, with a view to selecting additional countries where a Biotec presence will enhance our service to our clients.

EPM: Where do you think the company sits in the sector?

ML: Before I joined Biotec I described the company as the ‘best kept secret in the industry’. While we can’t claim to be a top three player in our market, our recent growth and investments are closing this gap.

Customers are impressed by the expansion they see - one told me he had considered us too small for his larger projects and was delighted to see how wrong he had been!

Our reputation was built on our expertise in temperature-controlled packaging and distribution. We are great believers in ‘if you do something well, keep doing it’ so this will remain a key part of our business. It’s too early to claim we are ‘the leader’ in this area but I think it is reasonable to say we are ‘a leader’. We have also focused heavily on emerging therapies such as cell- and gene-based therapies.

These are high value, often one-of-akind personalised medicines.

their business models and are increasingly outsourcing non-core activities. They have focused on the volume of work the industry outsources and the way they outsource. Most outsourcing used to come from Big Pharma with a lot of in-house expertise, so our role was to execute projects according to our clients’ instructions. Now the industry is more like virtual companies that expect greater input from their service providers. This creates pressure but also gives us the opportunity to show what we can do, which helps us develop closer relationships with our partners.

The recovery of the biotech sector after the recession of 2008 is great news. A healthy biotech sector cooperating with larger pharma is the key to a healthy long term outlook for our industry.

Finally, the emergence of regenerative and personalised medicine is a key development.

Some of the trial results for these new medicines are impressive and show great promise. Biotec has invested in developing facilities and expertise to support this growing area of research. Our partnership with TrakCel will produce the first product to support tracking of cell therapies throughout their chain of custody. This increases the availability of autologous cell therapies to patients by enabling industry to safely scale-up manufacturing process for these revolutionary medicines. It is great to be part of something like this, no matter how small that part may be!

EPM: How do you see the pharma sector in general?

ML: Many of the larger pharma companies have changed

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“

One of my first tasks on joining Biotec was to get a feel for how our clients view our service.

Feedback was excellent – 97% of our current clients would recommend us.

”

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On the up: The development of ready-to-fill sterile primary packaging systems in cooperation with leading equipment manufacturers has improved aseptic filling operations

OPINION

Trend hunter Dr. Johannes Rauschnabel, chief pharma expert at Bosch Packaging Technology, shares his view on some major trends in the pharmaceutical industry, and what they mean for equipment manufacturers.

What does the pharmaceutical future hold?

Shape of things to come: According to Dr. Johannes Rauschnabel, Bosch Packaging Technology, we will see markets across the globe implement new best practices and manufacturing concepts

I

ncreasing healthcare costs, new legislation and expiring patents call for decisive changes in the global pharmaceutical industry. New markets for specialty medicines, biopharmaceuticals and biosimilars are opening up, entailing opportunities for further growth.

The coming years will see markets across the globe implement new best practices and manufacturing concepts. What they all have in common is the need for safe, highquality and consistent operations.

Having left the best part of the generic patent cliff behind, the patents of several large, biotech molecules are now about to expire, opening the doors for biosimilar production. Biopharmaceuticals and their successors all require intensive research and development, as well as sophisticated equipment and contamination-free raw materials.

Moreover, the use of high-potency pharmaceuticals has grown extensively, causing manufacturers to pay more heed to protecting all elements of the supply chain from their potentially harmful effects.

Due to ever-stricter guidelines for aseptic filling operations, manufacturers increasingly rely on the use of isolators to reduce human contact with products. Compared with conventional cleanroom production, isolators offer higher product quality, lower operating costs and significant energy savings, as well as a safe accomplishment of longer production cycles. The development of ready-to-fill sterile primary packaging systems in cooperation with leading equipment manufacturers has improved aseptic filling operations and paved the way for the development of new, highly flexible filling and closing machines designed to handle presterilized nested syringes, vials and cartridges.

Manufacturers of solid dosage forms have also recognized the need for containment solutions. They require closed containers or biological cabinets, and the use of rooms with specially designed air handling and secure operating procedures. Some drug manufacturers have already built entire containment facilities, where building and equipment are optimally fine-tuned to one another.

Involving the equipment supplier at an early planning stage ensures flexible, modular and space-saving solutions.

A concept that benefits this approach is continuous processing.

Adopted by other industries many years ago, pharmaceutical companies only recently started to apprehend the benefits of continuous processing in terms of cost, time, space and material savings. As opposed to batch manufacturing, continuous processing implies manufacturing and processing materials without interruption. This concept will only work if it is based on a thorough understanding of the process interaction between the different unit operations. The FDA, for instance, strongly advocates continuous processing and has pointed out that the approach is consistent with the agency’s Quality by Design (QbD) efforts.

QbD aims at defining the quality and efficiency of a product before it is manufactured, and considers Process Analytical Technology (PAT) – building quality into products during the manufacturing process – as an integral part of QbD. With a comprehensive control strategy for material, process and end product, these approaches can lead to reduced product loss, less production fluctuations and faster time-to-market. When the FDA issued its PAT guidance in 2004, it triggered the development

EPM 14

of new technologies for the in-line elimination of variable product quality. Novel inspection devices, for instance for capsules, simultaneously inspect all quality features like weight, foreign particles and length in real-time and at high throughput rates.

Secondary packaging and end-ofline equipment also play a major role in ensuring pharmaceutical product quality. Many countries are currently developing and implementing new guidance and legislation to implement serialization codes for pharmaceuticals. The European Union’s Directive 2011/62/EU (Falsified Medicines Directive), for instance, stipulates the implementation of uniquely coded, serialized packs for almost all prescription drugs, while at the same time demanding tamperproof closures that indicate whether a package has been previously opened or tampered with.

Pharmaceutical manufacturers are facing major challenges to implement these regulations in time.

They must establish new procedures for the management and storage of serial numbers, which in turn requires the adaptation of highly sophisticated packaging processes in line with global strategies.

This calls for a complex software architecture that will integrate the serial numbers consistently on all levels – from devices, line processes and line management to production and enterprise control. A multi-layer and modular machine and software concept is obviously the safest option. It must be compatible with existing line concepts, allowing for the development of a complete system that complies with the industry’s overall demand for safe, high-quality and consistent operations.

IT’S GOOD TO TALK What will be the biggest challenge to the pharma sector in the next five years?

“

research.

We are in a golden age of medical an ongoing be Over the next five years there will ers of pay and ents pati challenge to convince icularly part s, tical ceu rma pha of e the overall valu t of men iron novel therapeutics, in a global env with pled cou ce plian increasing regulatory com . gets bud drug on downward pressure

care

Kevin Bottomley, Results Health

“

“

A healthy future in pharma depend s on biological pipeline success, whether alone or in tandem with small molecules.

The challenge lie s between platfo approaches and rm rapid, yet pragm atic adoption of improved proces s and analytical technologies to m diverse global m eet arkets. More flex ibility and faster evaluations will be necessary for ea ch new project.

Expanding adop tion of single-use technologies (SUT in biopharmaceu s) tical manufacturin g also presents a significant indus try challenge. It is balance the bene imperative to fits of SUTs, while ensuring quality consistency of th and e SUT compone nts and systems. will require a trans This formation in trans parency and GM partnership betw P een drug and SU T manufacturers .

”

The ongoing consolidations of companies and additional requirements of existing and new markets lead to higher demands on life-cycle-management of products especially make-or-buy decisions.

”“

Tony Orchard, P all Life Science

Nadine Reuter, Aesica

Eliminating solid dosage waste an d optimising supply chain reliability ar e Big Pharma’s gr eatest challenge s. With modular, reduce d-footprint facilitie s, continuous man ufacturing will fu rther personalised med icine (flexible ba tch sizes), enhance clinical trials (no scaleup), optimise man ufacturing quality (inline process co ntrols) and provid e an economically viable alternative to traditional manuf acturing models .

I believe that with increasing cost pressure and regulatory changes adversely impacting profit margins, there must be more emphasis on managing an integrated supply network both during development phases and into continued commercial supply, focusing on effectively mitigating risk, reducing lead times and ensuring total compliance throughout the product lifecycle.

Graeme McBurney, Almac

Frans Maas, GE A Pharma Systems

“

ess Pharma’s biggest challenge is proc Facing fundamental changes, Big , R&D nse inte inefficiencies. Besides more optimisation and manufacturing es lleng cha e thes port sup le-use technologies t innovative solutions such as sing men elop dev drug e ectiv t-eff cos ced risk and by offering greater flexibility, redu be to is tion , our challenge and contribu opportunities. As a leading supplier of high quality solutions. rce sou ble trustworthy and a sustaina

dim Biotech

Jean-Marie Cappia, Sartorius Ste

”

s

”

”

One of th e key ch our indu allenges str in molecule y is the increasin gly comp s coming le through pipelines developm x . ent are chall These potential treatm engin optimisin g in terms of form ents g ulation, b io availabil therapeu ity and th tic delive eir ry profiles, in terms a o treatmen f developing diffe s well as ts th ren patients, at are not only e tiated ffective fo but appre r ciated by and purc doctors hasers.

Will Dow nie, Catalen t

Globally addressing analytical outsourcing from product characterisation through quality control activities is a real challenge for bio/pharmaceutical manufacturers. Key success factors include proximity, expertise, time, and cost-savings without compromising quality, safety, and control. This is particularly challenging for companies outsourcing to Asia given the increased scrutiny by the FDA.

Frédéric Gaussens, SGS Life Sciences

EPM 15

EPM 16

NEWS ANALYSIS Marriage of convenience?

Stephen Archer, Spring Partnerships asks whether Pfizer and AstraZeneca is a marriage not to be – yet?

M View point: Stephen Archer, Spring Partnerships feels the Pfizer ambition for Astra Zeneca was over-reaching ambition with a hint of desperation

ergers and acquisitions may excite the markets and shareholders on both sides but their record of success in delivering the anticipated benefits is not good. Around 80% fail on costs savings and growth in shareholder value. Despite this, ambition, hubris and corporate desperation mean that boards often move with the heart rather than the head. Pfizer is a good example.

It has made acquisitions of $240 billion in the past 15 years and yet its current market capitalisation is just $189 billlion today.

of drugs quite aggressively as their own sovereign deficits have been under pressure in recent years and with healthcare a large and increasing cost to states.

Was the Pfizer ambition for AstraZeneca one of hubris? Actually I don’t think so. It was certainly over-reaching ambition with a hint of desperation. To understand the Pfizer move we need to consider the state of the pharmaceutical industry. It has been in relative decline for the past decade. Compared with 20 years ago the industry has fewer novel drugs and a weaker pipeline of new drugs. This is despite an annual global R&D spend of $88billion* per annum by the top 50 pharma companies. The costs of a new drug coming to market is now circa $1.3 billion but the painful statistic is that the return on R&D investment has halved in the last five years in round numbers.

Access to additional R&D pipeline projects, some of which may hold out high promise;

“

These factors threaten shareholder value and have pushed pharma leaders into protecting or trying to enhance shareholder value through mergers and acquisitions. The consolidation of the past 20 years has been huge. The motivation for these consolidations fall into the following categories:

Access to skills in R&D; Reduction in overall R&D spend; Strengthening presence in certain markets: eg. diabetes, heart etc. to build market credibility in these therapeutic areas; Access to new or more markets through additional sales channels; Synergies and cost savings in general operating costs; Access to new markets and new therapies to add to the existing portfolio.

In the next ten years we can expect the cost of getting drugs to market to rise and the potential for new drugs to be blockbusters and cure major diseases to remain a challenge.

”

This situation is something of a paradox given that research tools have advanced and doubly paradoxical given that the slowdown in drug innovation co-incides with the emergence of genomics as a mainstream science allowing companies to in theory to match compounds to individual genes and individual genomes, ie. a person’s unique gene constitution. The truth is that with advances in science have come complexity and cost. Managing R&D is very difficult. In the last decade this issue has been partly answered by the growth in pharma investment in outside organizations – biotech’s, research institutes and more who do the heavy lifting of research and can then pass the development and trialing back to pharma. But still the R&D cost is returning less for each pharma company. On top of that, two other pressures are working on the industry.

Firstly, as drugs come off patent then the generic copies come to market and decimate the product revenues of the patented version.

Secondly, the state health systems in most wealthy, mature economies have been pushing down prices

EPM 17

So as we see consolidation in the industry we will also see that R&D is consolidated and more outlying conditions being left behind as the fewer R&D functions focus on the drugs that will bring the best returns and most likely success in clinical trials.

In the next ten years we can expect the cost of getting drugs to market to rise and the potential for new drugs to be blockbusters and cure major diseases to remain a challenge.

So the good news is that diagnosis will improve for patients and smaller niche pharmas could come back into play as viable businesses though they, like the recent crop of biotechs will inevitably be swallowed by larger pharmas who will want to buy revenue streams and down stream profits as well as access to new markets and patients.

In the final analysis, I believe that competition through R&D innovation, better disease understanding, better diagnostics and more targeted compounds will lead to the emergence of new players in the market who can serve communities better than ‘big pharma’ is willing to risk doing.

R&D is going to get tougher to succeed in and returns may not improve but diagnostics and genomics will enable pharma in general to reach more people with more therapies. Until that time we should remain skeptical of the motives and effectiveness of pharma to serve the population.

* European Commission

Quality counts

CPHI PREVIEW French Dressing

For 40 years, Butterwo rth Laboratories has pro vided outsourcing solutions for quality co ntrol testing, method de velopment and validation and stability storage and testing. Th e company combines knowledge of QC testing with a pra ctical working for the development and validation of methods robust enough for QC purposes.

CPhI Paris takes place on 7-9 October at Paris Nord Villepint, offering the ideal opportunity to network with the global pharmaceutical community, source new suppliers, build relationships with existing partners and identify new business opportunities. The EPM team will be at the event and we’re looking forward to meeting up with you and discovering the latest developments you have been working on as well as the services you have to offer today’s pharma manufacturer.

Butterworth can also ass ist in the design of sta ndard real-time studies, stress testing over short periods at ele vated temperatures and photo stability stu dies, to comply with ICH guidelines. It welcomes customers to discuss their requir ements as well as making its analysts ava ilable for technical dis cussions.

Butterworth Laborato

ries, Hall 1, Stand F7

8

Roquette fuel

Celebrating 50 years of Partnerships Built on Innovation.

1964-2014

Roquette supplies actives and excipients. It provides guidance to make the best possible use of excipients through the development process -– from the creation of prototypes to scale-up. Its slogan “simply formulate your wishes,” highlights the level of support the company is able to provide.

Roquette’s excipients and actives meet a range of needs including: Direct compression or wet granulation; liquid formulation for syrups and suspensions; molecular encapsulation for a better solubility and taste-masking; polymers for tablet film coating and orally dispersible films; pyrogen-free raw materials for injectables and dialysis solutions and solutions for hard capsules filling and sachets.

Roquette Freres, Hall 5, Stand Q44 phillipsmedisize.com

EPM 18

Smooth operatowitrh the findings of

nd will be abuzz The Hermes Pharma sta suffering from the number of people its survey to estimate page 22 EPM) tablets/capsules (see difficulties swallowing ules exhibit nventional tablets/caps The study found that co many for ion t be the best solut drawbacks and may no lties cu fi dif ve ha le op rveyed pe people. Over 55% of su I an AP solely as capsules. By offering swallowing tablets or ies are ignoring an armaceutical comp a tablet or capsule, ph rtunity of po op an and missing their customers needs . ms for e ly dosag introducing user-friend

and P45 es Pharma, Hall 6, St

In hand Rigaku will be showca sing its new generation handheld Raman analyser for raw material identification (RMID).

Progeny is designed to deliver improved perfo rmance, ease of use and confidence in a handheld form.

Unlike other handheld Raman devices, Proge ny eliminates issues of fluorescence interfere nce with the use of a 10 64-nm excitation laser. enables users of hand This held Raman to measu re materials through thi coloured bottles, such ck, as polysorbate 20 and polysorbate 80.

Rigaku Raman Techno

logies, Hall 1, Stand

Herm

Salt of the earth Dr Paul Lohmann provides high-purity mineral salts to the pharmaceutical sector with more than 350 products and more than 1000 qualities, designed to provide optimum performance across a range of applications.

In the company’s GMP and ISO 9001:2008 certified facilities it produces minerals that comply with diverse regulatory requirements, current pharmacopoeias or custome r specifications. To support its cust omers in their registration efforts, it prepares ASMFs and has CEPs avai lable for a growing number of prod ucts.

Dr Paul Lohmann, Hall 6, Stand

F119

Growing poweDrcontract service supplier and bioreagent aceutical R& of lation and production Bertin Pharma, a pharm m2 facility for the formu 00 15 a n d so ire hn qu Jo ac & s n ha supplier, gs from Johnso the-counter (OTC) dru vices to clinical batches of overl also provide R&D ser wil y an mp co e Th F).

SB (JJ e nc Santé Beauté Fra JJSBF. of 80 employees and quisition, a workforce ac site ac s the rtill Ma BF With the JJS es, Bertin Pharma cover GMP-compliant faciliti l tica 2 eu ac arm ph of 3500m nt whole drug developme ng eri value chain, off ges solutions in full packa . ns sio ver e on -al nd sta or

Bertin Pharma, Hall 1, Stand H23

C82

pact m o c t i g n i p e Ke ct cus on compa nology will fo

ing Tech uipment for Bosch Packag showcase eq d an s em st eutical dosage laboratory sy solid pharmac d an d ui liq processing filling forms ries for liquid FHM 1000 se e hich th w b be la ill id w ol S On show ry device to ra bo la e th g, d e mixin operations an s, enabling th –2 kg batche l particles and al sm of handles 0.05 and coating g in at ating in ul an et gr and tabl co drying, d bed module ui fl e th in ts pelle ule. the coater mod and Head to this st n tli üt H to see the e th , ix m Mycro -shear smallest high or at ul mixer gran ry to ra bo in the la e ng ra t en pm equi ty es and the Man blet Xpress 100 ta ovides pr ch hi w s pres to ty an opportuni ns. blet formulatio ta w ne evaluate

hnology, Hall

ging Tec Bosch Packa Stand C38

Pure and simple Croda is a global player in specialty chemicals. An in-house proprietary flash chromatographic process is used to manufacture high purity super refined excipients for the pharmaceutical industry without altering the fundamental structure of the excipient.

Croda offers products for topical dosage forms, plus high purity multicompendial solvents, solubilisers and surfactants suitable for parenteral, oral and ophthalmic formulations.

Croda has EXCiPACT certification for its sites in Mevisa, Spain and Rawcliffe Bridge in the UK, and is following a global plan to gain accreditation at all sites supplying pharmaceutical excipients.

Climate control

New products include the ICH L climate chambers 260 and 750 which can be equippe d with a second illumination un it, doubling the space for stability tests of pharmaceutics in acco rdance with standard ICH Q1B, op tion 2.

The Memmert ICH ran ge offers two

Croda, Hall 5, Stand T76

additional models for stability testing. For tem perature testing, the ICH chamber works below zero temperature s, from -10 °C to +60 °C and from +10 °C to +60 °C with active humidity ranging from 10–80% rh. ICH C can be unive rsally applied for building material tes ts or for cell biology ap plications that require below room tem perature conditions.

Memmert GmbH + Co

. KG, Hall 1, Stand A7

EPM 19

1,

7

Identity parade

CPHI PREVIEW

B&W Tek says its 21 CF R Part 11-compliant Na noRam handheld Raman spec trometer is the ideal ch oice for nondestructive identifi cation and verification of materials by non-technical users in the lab, warehouse, loading dock or field.

Safe and secure

The NanoRam offers libr ary and method trans fer through updates to the NOS operating software and accompanying NID co mputer software. This allows methods and libraries developed on one Na noRam handheld unit to be tra nsferred to another Na noRam handheld unit for the ce ntralised development of libraries and methods across an organisatio n.

Schreiner MediPharm has developed the security solution FlexiCap, which clearly shows when a primary container has been opened. A label is combined with a cap, similar to wine bottles but which has been adapted specifically for the pharmaceutical industry.

Flexi-Cap can be used with different container types and sizes.

The label can be applied without using heat, so is suitable for temperature-sensitive medicines. The pharmaceutical manufacturer’s label and brand design remain unchanged, due to the combination of label and cap. The top of the cap allows space for barcode printing.

B&W Tek, Hall 1, Stan

d C72

Confidence boost

Schreiner MediPharma, Hall 2, Stand J40

manufacturing act development and Aesica, the global contr and API services to se do d he provides finis organisations. It organisation (CDMO), erging biotechnology em d an l tica eu ac arm leading ph cycle, from early-stage ges of the product life sta all at ise ert exp offers d supply. ercial manufacture an development to comm g ever-changing staff is capable of meetin lled ski its s say a sic Ae confidence with its d that customers gain ndards set by FDA, regulatory demands an stringent regulatory sta g etin me of ord rec y exemplar market approvals.

A in addition to other VIS AN d an DA PM A, EM

Aesica Hall 2, Stand

B9

In the bag Technoflex has developed a standard line of Inerta polypropylene sterile bags. Fitted with either one or two tubes, the bags are dedicated to aseptic filling. Their ‘butterfly’ design reduces the number of folds that form during filling and facilitates product flow.

For product traceability, a specific area on the upper part of the bag is set aside for laser marking. The volume of the bags (50–500 mL) allows the injection of gas (nitrogen or argon) for products sensitive to oxygen (immunoglobulins, albumin).

‘Boat ports’ welded directly onto the bag body replace the standard tubes. They guarantee tightness and avoid potential tearing when the outer packaging is opened. A twist-off is welded to the tubular part of the first boat port, and the second is welded shut. This system keeps the bag free of microorganisms after radiation.

French connection

A real pro

Groupe Batteur has five manufac turing sites located in Normandy and Brittany for contract manufacturing of pharmaceutical products.

The company guarantees product quality and strict compliance with quality regulations.

Skilled personnel implement rigo rous procedures, in accordance with GMP and ISO 13485.

Laboratoires Gilbert Normandy prov ides sterile unidose manufacturing exp ertise and blow-fill-seal technology for pharma ceutical products, and medical devices. It also offers multiproduct manufacturing for prod ucts in liquid, semi-solid and powder form, packaged under pharmaceutical control in vials, tubes, bottles and single-dose sachets or impregnated towelettes.

Groupe Batteur, Hall 1, Stand B29

Technoflex, Hall 2, Stand D58

Aptar Pharma wi ll unveil its Prohale for optimal patie r — the smart DP nt compliance. It I has been develo intuitive and sim ped to be ple to use by asth ma and COPD pa tients.

Prohaler’s novel powder dispersio n technology en consistent lung de ables position operating at relatively low pa inhalation flow ra tes. It requires th tient ree steps – open inhale and close the device, it; inhaling trigger s the release of a of medication an full dose d a dose counte r reminds the pa many doses are tient how left in the device.

Prohaler also ha s a patient safety feature to avoid double-dosing an any risk of d wasted doses.

B&W Tek, Hall 1,

Stand C72

Perfectly packaged

ufacturing container and a specialist in developing and man is ing kag Pac rma Pha ical Med Nolato ing from 10 mL up to standard products with sizes vary closure systems. Boasting over 350 bottles, cream dispensers, ure systems include ophthalmic 7.5 L, Nolato’s dispensing and clos technology. child-resistant and tamper-evident ture of primary packaging kaging solutions and the manufac The company offers bespoke pac as Class 7 and Class 8. It such standard for cleanrooms, ISO the with t plian com ms nroo in clea high-speed assembly and the sites, all of which offer the quality, operates out of several production and efficiently. capabilities of supplying globally

g, Hall 2, Stand F53

Nolato Medical Pharma Packagin EPM 20

FPS, the natural choice for the containment systems in the pharmaceutical industry

packaging synthesis

granulation drying

milling/micronization Isolators for processing high potent and/or sterile drugs Complete micronization systems

F.P.S. Food and Pharma Systems - via Vandelli, 20 - 22100 - Como - Italy - Tel. +39 031 543429 www.foodpharmasystems.com - sales@foodpharmasystems.com Micronization & Containment Solutions

EPM 21

SOLID DOSAGE COATING

O

ver 55% of people suffer from swallowing difficulties when taking tablets and/ or capsules, according to a recent market study commissioned

by Hermes Pharma. The study surveyed 2,000 people in the US and Germany and was conducted by market research expert Spiegel Institut Mannheim. The findings also pointed out that swallowing difficulties are likely to have a negative impact on compliance and identified the weaknesses of conventional tablets and capsules in comparison to alternative solid dosage forms.

The oral route has long been considered a simple and costefficient way of delivery, with most products being traditionally formulated as solid tablets or capsules. However, consumer habits and demands are changing. Today’s patients have grown accustomed to having freedom of choice and the benefits of convenience. They also enjoy instant access to a wealth of information, leading them to request specific products and treatments and becoming more involved in therapy decisions than ever before.

Hermes maintains that pharmaceutical products will need to appeal to a wider range of preferences, from treatment needs through to lifestyle requirements in order to deliver medical and commercial success in the future.

Widespread difficulty swallowing tablets/ capsules

It’s no choke A recent survey commissioned by Hermes Pharma has highlighted some key issues surrounding swallowing difficulties with tablets and capsules. Hermes discusses the opportunities of capturing market share with user-friendly dosage forms To overcome these difficulties, a worrying number of people had turned to breaking tablets before swallowing (32% overall) or crushing them up and dissolving them in water (17%), both of which can affect API release profile, bioavailability and medical efficacy.

The same issue would affect the 9% of participants who reported having chewed tablets/capsules before swallowing them. Perhaps most worryingly of all, 8% of people had resorted to not taking their medication at all in the face of swallowing difficulties (figure 1).

Swallowing not just a problem for the elderly Around 44% of participants 65 years or older reported swallowing difficulties when taking tablets/ capsules. Interestingly, an even greater number (70%) of younger people aged 16-34 also reported this problem. Tablet size was an issue across all age groups: Older people tended to highlight factors associated with tablet size as

being the most important cause of swallowing difficulties, whereas younger people also cited disliking the taste and odor of tablets/ capsules.

The study also looked in more detail at relevant product characteristics when selecting medications/ food supplements. 64% of the participants reported that products should be easy and comfortable to swallow. Next frequently reported characteristic was a pleasant flavour/odour (41% of people), with the ‘ease of integration into everyday routines’ cited by 38%. A third of the participants mentioned that the packaging should be easy to open.

User-friendly dosage forms for a better experience When respondents were asked to evaluate tablets/capsules and alternative dosage forms based on their experience, they consistently scored tablets/capsules lower than all other dosage forms for

Over half of the people surveyed (50% in the US and more than 60% in Germany) reported difficulties when swallowing tablets/capsules.

The overwhelming majority of these people did not report any similar problems with foodstuffs or fluids, indicating that this trend is specifically linked to tablets/ capsules. A variety of reasons were cited for these problems, but the most frequent were due to tablets/ capsules being too big, becoming stuck in the throat and having an unpleasant taste/odour.

characteristics such as ease of swallowing, sensation in the mouth, package opening and ease of intake.

Instant drinks scored particularly high across most criteria in the US. They were felt to be easy to ingest, do not require much time for intake and are easy to swallow.

Orally disintegrating granules (ODG) scored highly in regard to ‘opening the packaging’ and ‘integration into everyday routine.’ In Germany, lozenges received the best evaluation as participants deemed them to be easy to ingest and integrate into their daily routines.

ODGs scored highly when it came to integration into daily routines.

Key take-aways of the study Conventional tablets and capsules exhibit a range of drawbacks and may no longer be the best solution for large segments of the population. By offering products that are easy to swallow, convenient to take and taste well, companies can improve patient experience, increase compliance, and boost the effectiveness of treatment.

Dosage forms such as effervescent tablets, orally disintegrating granules, lozenges, instant drinks and chewable tablets are truly user-friendly. They allow healthcare companies to expand existing product lines, prolong product lifecycles, revitalize brands and at the same time grow revenues.

Figure 1. Question: What did you do to resolve your problems when swallowing tablets/capsules or to relieve the discomfort?

(Multiple responses were possible.)

EPM 22

SOLID DOSAGE COATING

A coat of many colours Colorcon explains the advantages of using colour when film coating oral solid dosage forms for paediatric medicines.

F

rom a recent survey conducted within the pharmaceutical industry1 by Colorcon, it was confirmed that oral solid dosage forms are a preferred choice for formulation of paediatric medicines (fig 1). With careful selection of an appropriate film coating system, paediatric products may be coated with a suitable colour while also providing mechanical integrity, gloss and moisture protection to produce a robust tablet that is effective and easily recognised by consumers and dispensers.

Table 1 US and EU Data 2-11 Years

12-18 Years

Opadry 203A Opadry II (PVA base) Opadry and Opadry II (HPMC base)

Colorcon has extensively reviewed US and EU databases, looking at the medicines currently prescribed for paediatric patients. Review shows that components used in Colorcon coating systems, such as Opadry and Surelease have Precedence of Use in paediatric medicines; as well as core excipients Starch 1500, StarCap 1500, Methocel, Ethocel and Polyox (Table 1).

Choice of colour For pharmaceutical products, colours are not governed in the same way as other excipients, with most areas of the world maintaining a list of pigments approved for use in medicinal products as part of regional legislation. These lists, however, do not distinguish between adult and pediatric medicines, which means from a regulatory view all approved pigments are permitted for use in paediatric medicines. In reality, it is apparent that pharmaceutical assessors will question licence applications where a young patient is exposed to unnecessary excipients, which could include pigments.

Figure 1 Film coating these dosage forms also brings further advantages, including the following: • masking objectionable tastes or odours2 • helping them to be more easily swallowed3

Colour plays an important role in the formulation of dosage forms, including those intended for paediatric use. Colour can be used to identify a specific product, distinguish between dosage strengths and different forms (immediate or extended release) of the same product. Colour, therefore, can contribute toward minimising medication errors, making a dosage form more appealing to a younger patient, or disguise an unattractive medicine to help improve compliance.

Pharmaceutical assessors expect applicants to perform and document a risk assessment as part of their dossier, which discusses the issues relating to differentiation and adherence and to explain the options employed to address them, including a justification of the use of colour and reason for selecting a specific colour.7

• helping to positively affect patient preference • differentiating the visual appearance of product to mitigate dispensing errors • improving packaging efficiency4 • prevention of cross contamination • reduced tablet breakage and chipping during manufacture.

Commonly used coatings with precedence of use in paediatric medicines Film coatings typically consist of three main components – polymer, plasticiser and pigment. Precedence of use for the polymer and plasticiser is reviewed here.

During the development of a paediatric dosage form the formulator must assess any risk associated with their formulation to ensure that an age appropriate dosage form is selected.5 This is to mitigate risk of noncompliance and ensure suitable excipients are selected.6 One way to assess an excipient is to evaluate its history of use in existing medicines prescribed for paediatric patients to identify whether there is “precedence of use”, applicable for children aged two to18 years old.

References 1. J. Walsh and K. Hughes, “Pharmaceutical industry approaches to the formulation and development of pediatric medicines,”EUPFI Poster 2013.

2. D. To, et al., “Investigation of taste masking performance of an aqueous ethylcellulose dispersion (Surelease ethylcellulose dispersion type B NF) on acetaminophen granules,” AAPS 2013.

3. C. Wilson, et al., “Modern tablet film coating and influence on ease of Swallowing,” AAPS 2003.

4. K. Hughes, et al., “Impact of film coating on blister packing efficiency,” AAPS 2005 5. S.A. Thomson, et al., “Assessing the acceptability of mini-tablets for use in children aged 2–6 years old,” Pediatrics 123(2), e235–238 (2009).

6. J. Breitkreutz J and J. Boos, Exp. Opin. Drug Del. 4, 37–45 (2007).

7. Guideline on pharmaceutical development of medicines for paediatric use EMA/ CHMP/QWP/805880/2012 Rev. 1

EPM 23

MIXING & BLENDING

High flyer: A 100-gallon dual shaft mixer model CDA-100 equipped with an air/oil hydraulic lift for raising/lowering the agitators

Powder perfect

R

oss dual-shaft mixers are designed to enable efficient powder dispersion and convenient batch temperature control in the manufacture of low to high viscosity formulations. Two heavy-duty independently-driven agitators, a high speed disperser and a two-wing anchor, deliver a wide range of shear levels and flow patterns that can adapt to the varying rheologies of solutions, pastes, gels, suspensions and slurries all throughout the mixing cycle.

Pictured is a 100-gallon dual shaft mixer model CDA-100 equipped with an air/oil hydraulic lift for raising/ lowering the agitators. Rated for full vacuum operation up to 29.5”Hg, the system produces smooth and air-free mixtures with a tight particle size distribution. All wetted parts are stainless steel 316 including the mixer cover. The disperser and anchor are driven by 15HP and 10HP explosion-proof inverter duty motors, respectively. Both agitator shafts utilize single mechanical seals with Viton O-rings.

The sawtooth disperser blade draws solids into a powerful vortex and disintegrates dry agglomerates as the low speed anchor continuously stirs the batch. This combination of mixing actions ensures a very thorough turnover – fresh product is constantly coming in contact with the disperser and materials around the periphery are continuously being scraped off the vessel surfaces.

Many sizes from 1 to 4000 gallons come as standard. Most DualShaft Mixers up to 300 gallons are supplied with a jacketed mix vessel mounted on casters. Finished product is discharged through a bottom ball valve by gravity or with the use of a hydraulic ram discharge system. A range of built-in control options are available, from simple variable frequency drives to PLC recipe systems.

In the mix

D

Clean & clear: According to Dec Group, the Batchmixer is particularly useful in pharmaceutical applications where active substances must be handled with no contamination

ec Group has developed what it claims to be the ideal mixing system that meets today’s standards while providing the ultimate powder mixing solution.

Dec’s Batchmixer is an in-line mixing system based on the Powder Transfer System (PTS) technology that can blend active substances without modifying their physical properties.

active substances must be handled with no contamination or physical property changes. It also allows operators to mix sensitive or volatile powders. The Batchmixer is also said to combine speed and reduced overall process time with the flexibility that enables the same unit to run widely varying batch sizes, from laboratory scale to largescale production.

The system transfers, mixes and discharges products fully automatically by vacuum and pressure under inert conditions. The Batchmixer is particularly useful in pharmaceutical applications where

The mixing system blends powders with large differences in blend ratios (1/10,000) and allows turn-down ratios to be varied from 10 to 100% of product load.

EPM 24

Efficiency all-round

T

he high shear mixer-granulator is crucial for the quality of granules. Density, stability and other parameters of the tablets depend upon this initial process.

The fluid bed is decisive for the throughput of the system, as it takes longer to dry the material then granulating it. Properly engineered transitions between the process steps are important for a quick and safe material transfer and an extra ordinarily high yield. Diosna’s CGS is designed and optimised to meet all these requirements, including the production of high potent granules.

The mixer is typically loaded by vacuum or gravity from IBCs. Stainless steel blow back filters on the mixer lid are cleaned in place (CIP) in line with the entire plant after production and a peristaltic pump in combination with a hollow cone nozzle guarantees for a very even distribution of the binder on the surface of the powders.

Following the granulation, the product is calibrated by a wet mill while it is transferred by gravity and vacuum conveyored into the drier.

The connection between wet mill and dryer is a short, straight pipe.

Also sticky granules are transferred fast, safe and without residuals into the fluid bed. The inlet connection of the dryer is installed right above the material bowl.

According to Diosna, by swinging the mixer discharge valve to the side, after CIP, the valve, the mill and also the impeller seal of the mixer can be inspected easily. The Diosna Toolift system raises the impeller up to 250mm. In lifted position, the shaft seal and the impeller from below are ready for inspection. This fits with Diosna’s design philosophy – WIP and CIP is always combined with ease of inspection.

The Diosna CGS system connects the mixer and the dryer technologically and mechanically and the fluid bed dryer is usually equipped for processes such as granulation and coating, making it a future proof system.

The drier including the charging and the discharging valve are pressure shock resistant (12 bar) and designed for efficient cleaning in place. The discharge valve is flushing with the wall of the material bowl. In case the binder contains organic solvents, also mixer and wet mill are 12 bar shock proof.

“

The Diosna CGS system connects the mixer and the dryer technologically and mechanically and the fluid bed dryer is usually equipped for processes such as granulation and coating, making it a future proof system.

Made to work: Diosna’s CGS is designed and optimised for the production of high potent granules.

”

1.

Objective Test Results

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THINK SMARTER ABOUT PACKAGE INTEGRITY INSPECTION Objective Test Results

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Test procedures are completely nondestructive enabling good product to be returned to the line.

Significant return on investment and cost savings can be achieved.

Laser, force decay and imaging inspection technologies ensure that no product or pack is damaged during the test process. Our equipment can detect weak seals, pin holes, capillary leaks and other pack defects down to 7 micron.

Our technology has been developed specifically for the pharmaceutical and medical industries. Test results are objective, reliable, repeatable and enable significant improvements in accuracy compared to destructive test methods.

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EPM 25

08/07/2014 11:16

LIQUID HANDLING

P

harmaceuticals are potentially hazardous and as such must adhere to stringent safety and legal requirements during transit, within nation states and across international borders. The correct labelling is an essential part of these safety procedures.

Safety first The potentially hazardous nature of liquid pharmaceuticals means that during transportation each consignment needs to be properly packaged and labelled. This helps to ensure the safety of everyone involved – the sender, carrier and receiver – and minimises potential risks. All labels and documentation have to conform to national and international legislation and should include information on the active ingredients as identified by their International Non-proprietary Names (INN).

Globalisation has increased the breadth and reach of international trade. The system of labelling has become increasingly complex and often dangerously misleading as people from different countries, speaking many different languages, come into contact with shipments of potentially hazardous goods.

To ensure a universal system of labelling, understandable to all, the United Nations has created the Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS).

Handle with care According to Hibiscus, correct labelling is essential for safe liquid pharmaceutical transportation This non-legally binding agreement has been designed to be less confusing but requires nation states and trading blocks to create their own legislation to implement it.

Throughout the European Union the CLP regulation (Classification, Labelling and Packaging of Substances and Mixtures) is a requirement for single substances and will be implemented on May 31, 2015 for mixtures, as part of this process.

Planes, trains & automobiles The type of product to be shipped, its purpose and destination will all have a bearing on the form of transportation chosen. Land is faster than sea and cheaper than air freight; sea is the cheapest option but takes time and air is the fastest method but is not suitable for heavy shipments. Reliability and security are essential for all consignments but refrigeration and hazardous goods compliance may also be required.

Pharmaceutical products can be dangerous for transportation,

particularly products such as cytotoxic drugs for cancer treatments as some may be flammable. Unless exemptions apply they are treated exactly as any other dangerous goods and are covered by the Carriage of Dangerous Goods and Use of Transportable Pressure Equipment Regulations, the CDG regulations, for journeys in the UK by road and rail. As with similar legislation the CDG regulations have been substantially restructured recently.

Dangerous goods transported by road in Europe are covered by the ADR. The latest amendments to this legislation came into force on January 1, 2013.

European rail journeys are controlled through the RID regulations and the IMO (International Maritime Organisation) is concerned with transportation by sea. The ICAO (International Civil Aviation Organisation) and the IATA (International Air Transport Association) regulate transportation by air. As legislation is constantly being updated and amended ensuring compliance can be complicated and time-consuming.

EPM 26

“

The potentially hazardous nature of liquid pharmaceuticals means that during transportation each consignment needs to be properly packaged and labelled.

”

However labels need to fulfil more than legal requirements. The size and content of each consignment, the destination, route and method of travel, as well as the expected environmental travelling conditions will all need to be considered in the design. Practical considerations, such as the ability to withstand extreme changes in temperature or prolonged exposure to seawater, are also relevant when deciding the type of label to use. The material, ink and printing process all have an impact on its durability. Every situation is unique and labels have to be suitable for each specific consignment. Bespoke labels can be designed and made to fulfil all these needs.

Balancing act

AX for Pharma develops and implements pharma software worldwide. As well as ERP, LIMS, plant maintenance / calibration and ABC costing, weighing and dispensing is one of the applications its product can be used for

harmaceutical companies face many challenges such as complex operations, advanced project and quality management, compliance with stringent regulatory requirements like 21 CFR Part 11 and EMA Annex 11 – and much more.

Too often, companies struggle and dedicate too much of their time and resources to build and customise systems that meet their needs and achieve FDA validation. AX for Pharma aims to meet the full range of ERP needs for pharmaceutical companies, minimise customisations and implementation challenges, providing expert support.

The capability to dispense materials error-free and with the precision required by product specifications is extremely important in the pharmaceutical industry. The AX for Pharma Dispensing module is fully integrated with Microsoft Dynamics AX 2012 R3 to cover the entire process from the formulation to the execution of dispensing operations in compliance with FDA and EMA regulations. It integrates with scales and barcode devices and generates labels and reports with an intuitive, user-friendly and modern user. A fully integrated dispensing module should reduce the chance of errors caused by allowing critical actions to be secured with electronic signatures, keeping electronic evidence of the history of these actions, which enables quick review and approval of materials.

Inconsistent data due to double data entry in manual and paper-intensive systems should no longer happen with this product.

The consistent quality of products is dependent upon proper proportioning of tested, approved materials. Materials are either selected for dispensing according to the FEFO or FIFO logic. AX for Pharma Dispensing module is designed to prevent the inadvertent use of nonconformant or expired batches.

The module provides global and material-specific processing rules and guidance to enforce standard operating procedures in the dispensing flow. It can manage potency adjustments, scale requirements and accuracy, weighing tolerances, operator training needs, MSDS and SOP reference links, material hazard warning messages, personal protective equipment requirements, suggested container size and quantity and weigh-scale calibration requirements. Support for electronic weigh-scale and use of barcode labelling technology help ensure the right material, in the correct quantity, with the right label, is delivered to production on time, for manufacturing.

The AX for Pharma Dispensing module manages the movement and control of all the dispensing batches and sub batches. Material to be dispensed is checked in real time to prevent the inadvertent usage and consumption of incorrect, expired, or rejected materials.

Regarding validation, this is a key aspect in regulated industries and dispensing is one of the most

P

critical processes in pharmaceutical manufacturing. AX for Pharma provides a cost-effective dispensing validation package with out-of-thebox validation documentation for IQ and OQ, with significant cost savings. In addition, the company’s validation specialists offer support in the validation of dispensing implementation.

EPM 27

WEIGHING This is a fully integrated solution aimed at providing a controlled, efficient, compliant and cost-effective dispensing process. The utilisation of raw materials and the operators’ tasks are optimised. Counter checks, label generation and inventory reconciliation are automated to increase the operator’s efficiency and reduce the risk of errors.

MANUFACTURING PROCESSES Money talks Why flexible filling lines and nested packaging are the front lines of pharmaceutical manufacturers’ search for cost savings by John Harmer, Vanrx Pharmasystems and Gregor Deutschle, Schott Pharmaceutical Systems

P

harmaceutical manufacturers today face a changing industry landscape. Advanced regulatory issues and new trends in medicine, such as personalised treatments plus the rise of highly sensitive biopharmaceuticals, are shifting needs within the pharmaceutical industry. Manufacturers are focussing on producing smaller batch sizes efficiently and many companies are turning their eyes toward filling line technology and filling line concepts. A flexible and fully automated filling line combined with nested packaging can accelerate production, minimise breakage, and lower total cost of ownership. For this reason, ready-to-use syringes have long been a staple of the pharmaceutical industry. These syringes are pre-sterilised and packed in nests and tubs to simplify the filling process by relieving pharmaceutical manufacturers from pretreating the syringe and installing sterilisation machinery.

Now manufacturers of pharmaceutical packaging and filling lines are applying these same efficiencies to other pharmaceutical packaging formats, such as vials. While pharmaceutical manufacturers could once support multiple filling lines to accommodate various drugs and packaging, it’s no longer efficient to change machine parts for different vial sizes or go to excessive time and money installin new filling line equipment. Manufacturers are seeking out packaging that is ready to fill and filled in an inherently adaptable system capable of fitting any packaging for any drug.

Team spirit: Vanrx and Schott have teamed up to adapt packaging concepts for filling technology needs to efficiently deliver drugs to market

This new imperative for flexibility in pharmaceutical packaging and filling lines is already being realised as new systems offer manufacturers a more efficient means of delivering drugs to market, accelerating the filling process, reducing breakage, and lowering total cost of ownership.

This evolution is being driven by the following goals: 1. Ready-to-use packaging. When syringes and vials arrive presterilised, manufacturers can eliminate the sterilisation processes — and the equipment needed to carry them out. Also, by reducing the number of machines, manufacturers consume less energy, save money on utility bills, and increase overall filling speeds and volumes.

2. A single standard. The nest-and-tub configuration developed for ready-to-use syringes offered an opportunity for other packaging, including vials. By using the same nest-and-tub format for multiple types of packaging, manufacturers can reduce the number of filling lines and equipment changes needed to produce various drugs, cutting the total cost of machinery and energy. Pursuing a single, standard method of filling both syringes and vials allows manufacturers to maximise the use of each filling line.

3. Full automation. Automation fills packaging more efficiently and reduces errors. For example, redesigning the stopper and closure portion of the filling line process could enable pre-sanitised closures to be applied to an entire nest of vials at the same time, speeding the closure process as well as saving companies from purchasing expensive closure sanitisation equipment. By reducing the total number of manual tasks, automation can cut overall energy costs to 25% of standard filling lines.

4. Inherent flexibility. Besides developing nests and tubs that enable manufacturers to fill drug packaging on a single filling line, nests that can fit different types and sizes of packaging avoid delays in production and reduce costs. Nests that grip vials by the neck, for example, can accommodate even non-ISO vials with different diameters, allowing manufacturers to switch the filling line to a different size vial without having to purchase new filling lines or change parts to accommodate a new drug or larger volume container.

5. A better process. One unnecessary complication in filling lines is damage to packaging through glass-to-glass contact. Nests that secure vials by the neck can prevent them from touching one another, reducing the chance of scratches or defects. These optimised nests can keep vials freely accessible on the bottom, allowing vials to undergo lyophilization with shelf-to-glass contact, improving conduction and eliminating the complexity of top-stem contact plates.

Pharmaceutical companies are seeking ways to increase efficiency and reduce operational costs. Pharmaceutical packaging and filling line manufacturers are answering the call by reimagining filling line solutions. It is imperative, however, that pharmaceutical packaging and filling line manufacturers work closely together to ensure efficient filling line processes. Vanrx and Schott have teamed up to adapt packaging concepts for filling technology needs to efficiently deliver drugs to market. The adaptiQ nest-and-tub system for ready-to-use vials combined with Vanrx’s SA25 aseptic filling workcell is one example of how these unions benefit pharmaceutical manufacturers by providing them with an integrated, highly efficient filling process.

As manufacturers shift toward ready-to-use packaging, opportunities exist to consolidate equipment and filling lines through a standardized, flexible system that helps manufacturers trim the total cost of their machinery and processes while more quickly delivering drugs to patients.

EPM 28

EPM 29

Warm front: C o

ntact plates a

CLEANROOMS

fter incubatio

n

Class monitor Andrew Barrow, Cherwell Laboratories offers an insight into monitoring cleanrooms and reducing contamination risk

P

harmaceutical cleanrooms are classified as class 5 to class 8 according to ISO standard 14644-1 based on number of particles of specified size per m3 air. They are graded A – D by the MHRA Orange Guide (EU Guidance on GMP) based on similar particle ranges at rest and in use, with additional limits for microbial contamination in operation.

The Orange Guide demands microbiological monitoring of air and surfaces in all four grades, with action and alert limits plus written procedures to prescribe corrective action if limits are exceeded.

The purpose of controlled environments and cleanrooms in particular is to limit the potential for contamination of product. For aseptic filling of sterile products in Grade A zones, the highest level of control and assurance is essential.

Support areas and production areas for non-sterile or pre-sterilisation materials must also be controlled and monitored.

Managing zero cfu In a perfect world there would be no growth on all the environmental monitoring plates from Grade A and very rare, or possibly zero, growth in Grade B. This will bring new concerns for quality assurance and inspection, with questions which include: How do you know your monitoring is effective – are the culture media and incubation conditions appropriate? How do you meet the requirement for trending results if everything is zero?

Monitoring the adjacent Grade C & D areas and the ungraded external support will help, as any potential contaminant in the Grade A can only be introduced from outside. Monitoring these areas where moderate counts are allowed and expected will enable the facility to establish the types of microflora commonly present in the local environment and highlight changes to the frequency or predominance of species close to the cleanroom. This knowledge can be used to modify cleaning and disinfection routines and chemicals to address any potential rise in bioburden levels before they put the production or filling area at risk.

Fundamental monitoring considerations There are many scholarly articles on methods, materials and sampling plans. The essential requirements include: • The sampling method; air sampler, settle plate, contact plate, swab, rinse fluid, etc. should have acceptable collection efficiency.

• The culture medium must be able to support an appropriate range of microorganisms. If there are known inhibitory substances, such as disinfectant residues or antibiotics, the medium should contain effective neutralisers.

• Sample size should be consistent and reproducible. i.e. surface samples, whether contact plate or swab, should be a known area; active air samplers should be calibrated to deliver a known volume; and settle plates should be exposed for a set time.

• Sample locations and frequency should be identified and chosen according to risk analysis, as well as regulatory requirement. This is relatively straightforward in high risk aseptic process operations in grade A zones because there are well documented expectations, as well as a requirement for investigation into every breach of action limit. In Grade C/D and ungraded support areas there is more scope for interpretation of expectations.

Using selective media The essential requirement of microbiological monitoring is to demonstrate compliance with regulatory expectations and in many cases is part of the batch release review process. The benefits can be much wider and contribute to the overall process improvement and risk reduction for both sterile and non-sterile products.

Routine surface and air samples in support areas after cleaning can reveal trends that might indicate a deficiency in the disinfection process. For example, if counts increase or spore forming bacteria are identified in a particular area, the cleaning can be reviewed early and sporicidal disinfection of this and any associated higher grade areas can be considered before any counts are found in the cleaner areas. Similarly, if moulds are found on air or surface plates with no obvious source of contamination, it might be appropriate to sample outside this room using selective media. This will identify the source and enable targeted cleaning before it becomes a threat to the production area. This approach using different selective media can be employed for other objectionable organisms in the production of nonsterile products.

The appropriate performance and presentation of media is essential for confidence that it will detect an appropriate range of organisms and that it does not bring any risk of contamination into the cleanroom. Some on-site validation is necessary, although choosing a media supplier who understands microbiology, decontamination and air sampling will help.

In conclusion A well-planned and implemented environmental monitoring (EM) programme is essential. By producing trending data, an EM programme enables the proactive management of contamination issues before they become critical, which ultimately saves money and crucially ensures safer products.

Results driven: The SAS air sampler enables microbial results as cfu/m3 (colony forming units per cubic metre) using the direct, multi-point impaction method onto a standard agar plate EPM 30

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EPM 31

28.07.2014 15:11:41

BIOAVAILABILITY

L

ow solubility of new chemical entities (NCE) is a welldocumented phenomena; it is estimated that between 40-70% of the NCE should be regarded as poorly soluble (ie. BCS class 2). Despite the high yield of poorly soluble compounds, potentially caused by the high throughput screening of target driven candidate selection, the utilisation of enabling technologies to improve bioavailability is limited (around 15% of the poorly soluble molecules). The reluctance to apply advanced formulation approached is related to the one hand the time pressure in projects around First-inHuman studies and the challenge that there is no single enabling technology suitable for all APIs and that predictability of the success of these technologies is relatively poor.

Therefore, multiple technologies are being utilised to provide an increase in bioavailability.

The most established approaches for improving solubility – solubilisation or complexation, particle size reduction, lipidics or utilising the amorphous state are described below. Combinations of these approaches are also possible and there are novel techniques emerging.

Particle Size Reduction Reducing the particle size of the API and therefore increasing the surface area by milling or micronising is routinely the first step taken in improving the dissolution

Soluble solutions Jon Sutch, manager of formulation Patheon, Milton Park, discusses flexible solutions for poorly soluble drugs rate of a molecule. In fact, this approach, because of this potential dissolution enhancement is often advantageous in combination with the other techniques. Reducing the particle size further, to the nano range can give a significant increase is dissolution rate and potentially therefore bioavailability.

The challenge is firstly producing the particles and then stabilising in a suitable oral formulation.

Bottom up approaches such as controlled crystallisation or top down techniques such as milling or microfluidics can be employed to create nanoparticles and typically surfactants or polymers are used to stabilise.

Solubilisation and Complexation The use of pH modifiers for ionisable APIs is a common technique employed for molecules with reasonable solubility at some point over the physiological pH range. This can be used for solutions and solid dosage forms but it is important to ensure the microenvironmental pH is maintained throughout the GI tract.

Complexation with cyclodextrins can also be employed in both solution and solids forms. The former is more common in a preclinical setting, whilst techniques to enable the latter whilst ensuring

complexation, rather than simply a physical mixture is an area of growing interest. A disadvantage of cyclodextrins is the large weight of these molecules, especially when improvement in API solubility often requires a molar ratio of at least 1:1, limiting drug loading and increasing dosage form size. The size, if any, of the solubility enhancement is also difficult to predict, but in some cases the increase is very significant and so they remain a key tool.

Lipidics Lipid-based formulations can enhance bioavailability either through improvements in wetting, formation of micelles, by encouraging absorption by the lymphatic system or a combination of all. Development of a lipidics system usually starts with a screen of lipids, co-solvents and surfactants. With these data the class of lipidic formulation can be identified and optimised. Depending on the solubilities achievable, a liquid fill in a hard capsule may be pursued usually as a solution but there is evidence a lipidic suspension may also provide bioavailability advantages.

Amorphous Formulations Utilising the potential increase in

EPM 32

solubility from the amorphous state as a result from the lower energy required to break-up a disordered system is an increasingly popular technique. The key is stabilising the molecule in this energetically unstable state, and a range of polymers have been shown to be useful in this regard. However, again the suitability of a particular polymer for a specific API is not easily predicted, although the use of solubility parameters is useful. Common techniques for amorphous systems include spray drying and hot melt extrusion. Both techniques have advantages and disadvantages, and it is useful to be able to investigate both to ensure the right fit for a particular molecule. The main challenge with this approach is stability of the API in the polymer matrix and the drug loading.

As can be seen there are several potential approaches with advantages and disadvantages and different APIs will be amenable to different techniques. There are many companies that specialise in one of the techniques listed below, but few will screen multiple solutions and therefore enable a successful path for development to be identified as quickly as possible. Due to the lack of predictive science in this area it is advisable to screen multiple approaches in parallel (such as Patheon’s SoluPath Flex) in order to reduce development time and to maximise success to identify the technology most likely to enable a new chemical entity.

EPM 33

The concept of digital health is becoming increasingly significant.

A recent survey has highlighted its importance on the pharmaceutical sector, the ways it will impact on current ways of working and asks will business models be reshaped by digital health?

DIGITAL HEALTH

Let’s get digital

R

esults from a recent study conducted by Arthur D Little and Karlsruhe Institute of Technology indicate that by 2020, the business model of the pharmaceutical industry will be transformed by digital health.

The changing market environment will come with promising opportunities for established pharmaceutical companies to participate in a highly attractive and innovative segment. So far, digital health solutions have not quite delivered on their promise.

Three elements are prerequisites for a successful engagement in the digital health space: • The definition of a digital vision and a comprehensive digital strategy: As long as digital initiatives and prototypes are only conceived in marketing departments and remain disconnected from the wider corporate strategy, the risk of failure is high • Offering real value to the patient: Solutions have to target unmet needs and improve the human condition with a disease, utilising the full potential and spectrum of digital solutions • A tailored approach to innovation: Redesign innovation metrics for digital health developments and offerings and no longer apply marketing metrics / company ROI hurdles that are commonly used to compare and prioritise investments in the healthcare industry

Principles of winning solutions A winning digital solution reflects the whole customer journey and targets specific interactions in the healthcare system. By connecting the patient, physician, payer, healthcare provider and supplier, easier communication between the parties involved occurs. The physician is crucial to the digital health value chain and could drive patient behaviour. Pharmaceutical companies

have an inbuilt association with doctors and could be in a stronger position to drive the adoption of digital solutions through the clinicians if their offerings address the doctor’s needs.

Medical device companies have not interacted with clinicians as effectively in the past, and would have to build related capabilities. There are eight principles to assess whether digital offerings have what it takes to create winning solutions:

Added value Addressing a patient’s needs and creating additional value for them as a customer. A smart solution improves the quality and outcome of a treatment by simplifying processes and saving time and money. The starting point should be the actual disease – how it impacts the patient’s life and the recommended treatment pattern.

Digital solutions should support the patient in tracking health and sharing data with physicians, renewing prescriptions and predicting changes based on data.

Platform/connectivity: A good solution uses a multi-channel approach to satisfy each patient’s demand. Social media, websites and apps offer are ways to the customer. Connectivity links the patient’s devices, transports data and allows a view of the patient in real time.

Data: Digital solutions collect and take advantage of user data. Electronic health records offer the possibility of tracking and sharing the patient’s health status and customising treatment. The data is already there today – why not use it and make it accessible to the involved parties to benefit the patient?

Intelligence: Superior offerings are going way beyond data collection. Intelligent systems make use of individual and patient group data to identify and

EPM 34

track changes to their health status in real time.

By considering external factors, treatments and solutions become predictive instead of reactive.

Only when an underlying understanding of interrelated variables exists can the app itself embed the algorithm.

Device: Winning digital health solutions require a device that collects and analyses the data, communicates with the patient and provides multiple interfaces to other medical devices and platforms. The device must be able to become a lifestyle product for the patient.

Sensor: Sensors enable tracking of a patient’s health in real time and yield precise measurements.

They mitigate the gap between home care and professional equipment. Sensors should be designed to be convenient – wearable, inconspicuous and suitable for daily use.

Pharmaceutical: Digital offerings can potentially enhance the value proposition of a pharmaceutical and the related therapy. Technological dimensions can add to the core product and enable a tailored treatment.

RFID chips on pharmaceutical boxes, sensors on inhalers, pumps, smart pills, cloud-based patient records, video platforms, patches and implants to track the status – for example – of the cardiovascular system or glucose concentration, learning programs, and many more options are available to enrich the value proposition.

Regional: Finally, winning digital solutions cannot be developed as one-size-fits-all solutions. In fact, the most successful offering will reflect the regulatory and care environment in each respective region. Not only will it understand, but also accept local pain points and accordingly adjust its value proposition.

Reddy made

HIGH POTENCY FACILITIES

Dr. Reddy’s Custom Pharmaceutical Services (CPS) explains the integrating of highly potent drug substance and drug product manufacturing

H

igh potency active pharmaceutical ingredient (HPAPI) production is the fastest growing segment of the pharmaceutical market. Specialist facilities and expertise are needed for the safe manufacture of high potency drugs. Dr Reddy’s Custom Pharmaceutical Services (CPS) offers integrated drug substance (DS) and drug product (DP) development and manufacture of highly potent compounds. An integrated manufacturing chain means that all the processes are carried out within one organisation.

This requires facilities where the DS and DP processes can be interlinked allowing for symbiosis of expertise. Streamlining the manufacturing chain by integrating processes has several advantages for the customer, such as risk mitigation, reduced time-lines and cost effectiveness.

Handled with care: CPS has modern facilities designed to handle highly potent DS and/or DP development

One Expert Team

Two Industry Leaders Have Joined Forces.

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Dr Reddy’s Custom Pharmaceutical Services (CPS) offers integrated drug substance (DS) and drug product (DP) development and manufacture of highly potent compounds. An integrated manufacturing chain means that all the processes are carried out within one organisation.

”

CPS has modern facilities designed to handle highly potent DS and/or DP development and manufactures at its sites in Vizag and Hyderabad, India. CPS can handle steroids and prostaglandins at various scales and manufactures at its facilities in Mexico and the UK. The manufacturing facilities are (FDA and EMEA) approved for supply to regulated markets for worldwide distribution. The site has standard operating procedures on how to handle material from an occupational exposure-limit perspective, with the goal of protecting the people, environment and the product from crosscontamination.

PCI welcomes the services of PENN Pharma.

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© Copyright 2014 Packaging Coordinators, Inc. All Rights Reserved.

AndersonBrecon (UK) Limited trading as Packaging Coordinators, Inc. is a company registered in England and Wales with company number 02543975 and VAT registration number GB 549 7026 19 whose registered office is at The Broadgate Tower, Third Floor, 20 Primrose Street, London, EC2A 2RS

EPM 35

DIGITAL PHARMA

The in cloud Rik van Mol, vice president of R&D Strategy at Veeva Systems explains the key considerations for those contemplating the uptake of electronic trial master files

T

ime is money, and never has the cliché been more apt than for life sciences companies seeking regulatory approval for a new therapy. In 2010, McKinsey & Company published a report which found mismanagement of the trial master file (TMF) is responsible for slowing down trials an average of 12 months, costing a provider up to $2 billion in lost revenue for a blockbuster therapy.

Setting aside the costs of failing to maximise sales opportunity, as regulators set the bar higher for Standard Operating Procedures (SOP) compliance and prepare their own systems for electronic submissions, the actual costs associated with maintaining a paperbased clinical TMF are steadily rising.

Facing this reality, nearly two-thirds of the industry has yet to move to a purpose-built electronic trial master file (eTMF), according to recent research conducted by Veeva Systems. So what is preventing more drug developers from taking advantage of eTMF applications that would streamline many of the inefficient processes that can slow clinical trials?

Getting everyone on board One of the biggest hurdles companies face when making the transition to paperless TMF is the creation of a collaborative system that all stakeholders in the drug development process can access easily and securely. The growing number of trial stakeholders (CROs, trial sites, agencies, committees, and patients) has increased the complexity of assembling the numerous trial documents into a coherent package. More sponsors are choosing to work with fewer

Processes That Would Shorten Clinical Development Times if Paperless 64%

Study/Site Start-up 54%

TMF Filing Study Planning/Protocol Authoring

Avoiding noncompliance

43%

Country Start-up

31%

Country/Site Feasibility

30%

Site Close-out

28% 26%

Study Close-out

25%

Drug Accountability

Fig 1.

*Source: Veeva Systems, The Paperless TMF, An Industry Benchmark 2014

CROs, and run multiple trials together. Both benefit from using a shared system, which, once defined, can be reused from study to study.

However, even in those cases in which the sponsor or CRO maintain an eTMF on their own network, the burden of paper becomes a significant drain on resources and efficiency. In this scenario, stakeholders send documents via paper shipments or email and maintain separate copies of TMF documents that they must reconcile at the conclusion of the trial. By contrast, cloud-based eTMF applications are easily and securely accessible by all parties.

Sponsors can define more efficient processes upfront, maintain visibility throughout the trial, and help ensure the TMF remains inspection-ready at all times. This type of collaborative and open process begins by uploading a document into a cloud eTMF.

Building a stable and replicable model Building a repeatable TMF framework involves reaching consensus on expectations from

the beginning, to ensure all TMF stakeholders are aligned on what the TMF artifacts are called, when they are due, and who is responsible for filing them. In order to know what content is missing or late, all contributors must first understand what is expected. A repeatable framework sets these parameters at the outset, reinforces the collaborative process, and improves overall efficiency.

Standardising a common nomenclature drives better communication by harmonizing the filing efforts of diverse stakeholders.

When multiple parties refer to items by different names (Figure 1), filing and tracking become confusing, increasing the chance for error. The nomenclature defined by the Drug Information Association (DIA) TMF Reference Model represents input from hundreds of pharmaceutical companies, CROs, regulatory agencies, and vendors from across the globe. In addition to providing industry standard language and naming conventions, the TMF Reference Model introduces new guidelines for content, structure, and metadata. For these reasons, more clinical trial sponsors are leveraging

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this model to build their own repeatable framework. In many cases, however, the sponsor and/ or CRO still maintain the eTMF on their own network, blocking access to outsiders.

With increasing regulatory pressure on life sciences—including new demands to enable remote monitoring of trial master files— organisations are seeking new ways to improve inspection readiness and make TMFs accessible to auditors on demand. To meet the growing expectations of health authorities globally, organisations are rapidly adopting eTMF applications in the same way that they once moved from paper case report forms (CRFs) to electronic data capture (EDC). The growth trend here is tremendous. These applications allow TMF owners to define standard operating procedures (SOPs) for how any clinical document is managed, and therefore flag any mismanagement early. By creating rules and definitions for SOPs, the eTMF is creating ways to track application workflows and identify noncompliant processes before the TMF is put before regulators for approval.

Act now – save time and money The urgent need for greater visibility into study conduct and quality benchmarks for trial operations is driving the industry’s growing use of new technology. The closer life sciences organisations come to operating a single source of shared electronic documents, the more value they can create in the development and approval of a new therapy.

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“

HIGH PROTEIN ANALYSIS

MSIA represents a fast, convenient and highly reproducible method for the enrichment and mass spectrometric analysis of targeted large biomolecules, including proteins, peptides, and antibodies.

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T

he large-scale study of proteins, or proteomics, looks at entire collections of proteins present in an organism, tissue or cellular/sub-cellular system.

Numerous branches of proteomics are finding applications in fields that span medicine, human health, drug production, the food industry and biodefense.

The science of proteomics has developed substantially over the past decade, building on different technological advances. Key to any proteomics experiment is the reduction of complexity in biological samples, removing highly abundant components of the proteome while enriching those in moderate to low abundance, and producing concentrated pools of the proteins of interest. In clinical applications and biomarker discovery, the most successful enrichment methodologies hinge on targeted selection of specific families of proteins, allowing the necessary sensitivity for the analysis of tissue extracts and biofluid samples. Mass Spectrometric Immunoassay (MSIA), in particular, is proving especially useful for screening biofluid proteins for micro-heterogeneity, providing a unique methodology that bridges the gap between global proteomic approaches (where full-length protein information is lost during obligated proteolysis steps), and conventional immunoassays like ELISA and RIA (where full-length information is preserved, but structural changes present in micro-heterogeneous protein pools can not be detected).

MSIA represents a fast, convenient and highly reproducible method for the enrichment and mass spectrometric analysis of targeted large biomolecules, including proteins, peptides, and antibodies. The method is based

Protein shake Cara Cesario, product manager, MSIA consumables & platform, Thermo Fisher Scientific, discusses MSIA – the answer to large molecule bioanalysis

on the isolation of biomolecules of interest with immobilized affinity ligands. After affinity selection, the bound intact biomolecules are released and analyzed using mass spectrometry (MS). The affinitybinding enrichment step provides increased assay sensitivity, while mass spectrometric detection provides great specificity combined with the ability to differentiate variations within the targeted protein pool. The MSIA methodology can support sensitive multiplex workflows capable of analysing simultaneously several targeted proteins and their variants (like point mutations, post-translational modifications, and truncations). It offers improved signal-to-noise ratio, protein recovery, and reproducibility, while allowing enrichment down to the picomole level.

The MSIA workflow starts with an affinity purification step. To simplify the method, porous solid supports called microcolumns are secured into the distal end of pipette tips (Disposable Automation Research Tips, or DARTs), to which antibodies and other affinity ligands are derivatized and covalently bonded.

MSIA DARTs are easy to use and offer multiple advantages. They are available in racks compatible with automated and semi-automated liquid handlers, saving time by enabling automation of workflows.

Unlike conventional automation tips, MSIA DARTs can be obtained in disposable rigid magazines.

When used in combination with the Thermo Scientific Versette automated liquid handler, they are sealed onto the pipetting heads by pressing against silicone pads, minimising volume displacement, while allowing consistent dispensing and ensuring tip straightness for improved well access. They also generate cleaner MS data, thanks to the microcolumn technology that reduces matrix loss and reagent carryover. MSIA DARTs are now available in a range of formats to support individual assay development needs, with binding systems based on streptavidin, insulin, protein A/G, or immobilized antibodies of choice.

After loading the enriched sample onto Liquid Chromatography / Mass Spectrometry (LC / MS) instruments, software solutions enable the analysis of biomolecules and protein modifications by comparison against protein databases. Quantitative measurements can be also obtained by matching against internal standards.

MSIA workflows can be validated and verified very quickly, and are finding an increasing number of applications. In the field of metabolic diseases, for which the analysis of insulin is central, there is an increasing trend to assay insulins

by LC-MS to analyze structural differences among insulin variants, something that would not be possible with traditional immunoassays. The coupling with purification by MSIA Insulin DARTs allows the development

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of novel multiplexed research methods for high-throughput quantification of native insulin and its therapeutic analogs in clinical samples.

Another MSIA-supported workflow that is finding increasing applications is the analysis of therapeutic antibodies. The development of monoclonal antibody therapeutics is on the rise and new bioanalytical methods are required to purify and analyze this new class of drug molecules. MSIA Streptavidin DARTs are covalently derivatised with streptavidin and enable the capture of biotinylated antigen ligands. By forming an immobilised streptavidinbiotin complex, desired therapeutic antibodies are purified by binding to their immobilized antigen binding partner. Because the monoclonal antibodies are purified as intact molecules, complete sequence information is preserved during MS analysis. MSIA Streptavidin DARTs are convenient, ready-to-use tools that offer flexibility to purify specific target analytes by using biotinylated ligands (antibodies and proteins).

Conclusion The proteomic analysis of biological samples presents unique challenges. The increasing need for high-throughput techniques involving MS is generating a high demand for automated, streamlined sample preparation tools for protein and peptide extraction. The advent of new MSIA technologies and approaches can detect and quantify proteins and variants down to picomolar-levels with excellent reproducibility. Processing and analysing samples in less time with increased high throughput and robust results is paving the way in biomarker discovery and analysis.

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EU cooperation with international partners on generics Chetan Javia is ELC Group’s regulatory affairs expert in India

T

he International Generic Drug Regulator Pilot (IGDRP) was launched in April 2012 to promote collaboration and convergence in generic medicines regulatory programmes in order to address the challenges posed by increasing workloads, globalization and complexity of scientific issues.

The European Union (EU), using the DCP (Decentralised Procedure) as a model, is leading an international pilot project through which, upon request from a generic pharmaceutical company, it will share the assessment reports generated as part of the DCP assessment procedure in real time with collaborating regulatory agencies outside the EU. The first phase of this project involves the EU, Australia, Canada, Chinese Taipei and Switzerland.

Other members of IGDRP – which includes Brazil, China, Japan, Korea, Mexico, New Zealand, Russia, Singapore and South Africa – may decide to take part in the pilot programme at a later stage.

A generic drug applicant wishing to market the same ‘generic’ product in the EU through the DCP and in other jurisdictions that form part of the IGDRP are invited to participate in this pilot programme,

provided they fulfil the eligibility criteria which are: synchronized filling of the application in at least one of the IGDRP member states; no major safety, efficacy or quality differences; complete compliance with the regulatory requirements of the participating countries, including those of in-vitro and in-vivo comparative studies; completed Summary of Quality Differences form; consent granting permission for the sharing of the DCP assessment report with non-EU agencies; and prior experience of DCP submission.

The DCP Pilot will involve a parallel review process, with non-EU agencies continuing to conduct separate but synchronised receipt, validation/screening, assessment and approval or refusal steps, using the outputs from the Assessment phase I and Assessment phase II of the EU DCP. [Figure 1]

Figure 1

An Expression of Interest (EOI) to participate in an information-sharing pilot for the evaluation of Generic drug applications (restricted only to immediate release solid oral and oral or injectable solutions) was issued on 23 July 2014.

criteria, templates of consent forms and the Summary of Quality Differences form, plus a schematic of how the DCP Pilot would operate and the contact points for submission of this EOI, please refer to the CMDh (Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human) website (http://www.hma.eu/cmdh. html).

For details regarding the information to be provided in the EOI, eligibility

Interested applicants should inform the contact points of the candidate

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agencies selected by the applicant and the CMDh secretariat at least eight weeks prior to the intended submission date using the EOI form.

Applicants should also inform the proposed Reference Member state (RMS) of the DCP and the CMDhMember of that member state about their intention.

The deadline for submitting the EOI application is September 26th 2014.

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

Aiming high Miroslav Reljanovic, CEO, Ergomed, has great plans for the company.

Offering specialised services for the pharma sector, he believes the business is set to become a leading global provider of pharmacovigilance, and medical information

EPM: Who are you and what do you do?

MR: Ergomed was set up 15 years ago after identifying a growing need to run clinical trials for testing drugs more effectively and more efficiently.

Today, Ergomed is a profitable UKbased company dedicated to the provision of specialised services to the pharmaceutical industry and the development of new drugs, working primarily in clinical development, late phase development and rare diseases. Ergomed has a global footprint, operating in over 40 countries across five continents and has more than 60 clients ranging from top 10 pharma companies to biotechnology companies.

We have two complementary businesses; the services business which is a well-established, clinical research business and a postmarketing services business and the co-development business, which has a growing portfolio of partnerships with pharmaceutical and biotech companies. In these partnerships Ergomed is providing its drug development expertise on a selected basis in exchange for a carried interest in any revenues attributable to the drug asset, including outlicensing milestones as well as sales of the product.

EPM: What have you been focussing on recently?

MR: Ergomed recently listed on the London Stock Exchange’s Alternative Investment Market (AIM), and acquired sister company PrimeVigilance, which specialises in pharmacovigilance. This has been an exciting time for the company and we are now well positioned to grow the company and build further value.

We believe that the support shown by our new investors is testament to their understanding of the growth potential of our core services business and the value to be created from our co-development business. This listing provides a great opportunity to expand and accelerate our growth as we look to become

one of the leading global providers for rare disease/orphan drug development services, post marketing services and to expand our portfolio of co-development partnerships.

PrimeVigilance was recently awarded the Queen’s Award for Enterprise 2014 in Recognition of Substantial Growth and Commercial Success.

Q & A

EPM: What is your latest service/ innovation?

MR: Ergomed has particular expertise in oncology, neurology, immunology and the development of orphan drugs. We believe our approach to clinical trials is differentiated from that of other providers by our innovative study site management model and the use of Study Physician Teams, which results in a close relationship between Ergomed and the physicians involved in clinical trials.

Additionally, our co-development business model is a market leading opportunity for capital appreciation though participation in drug development. Ergomed has completed seven deals to date providing drug development services as a significant contribution in kind in exchange for an interest in the potential future revenues attributable to the drug assets.

As part of an agreement, Ergomed will typically carry out all aspects of the clinical trial, including input into planning and design, while the partner retains responsibility for CMC, IP and commercialisation.

However, Ergomed has a flexible approach and deal terms and structures vary depending on the compound, development plan and commercialisation strategy.

To date, Ergomed has signed seven co-development agreements with a range of partners including the current active deals with Aeterna Zentaris, Synta, CEL SCI and Ferrer.

EPM: How can you benefit the pharmaceutical sector?

MR: Ergomed provides specialised services to the pharmaceutical

Leading the way: Among other things, Ergomed’s medically led approach to the planning and execution of clinical studies is suited to orphan drug development studies, says Reljanovic

industry, through clinical development as well as through our co-development model.

Through PrimeVigilance, we are the leading provider of drug safety (pharmacovigilance) and medical information services creating a broader service offering to healthcare companies.

EPM: Future plans?

MR: We have a clear growth strategy to become one of the leading global providers for rare disease/orphan drug development services. Ergomed’s medically led approach to the planning and execution of clinical studies is

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particularly suited to orphan drug development studies because of the difficulty in recruiting patients and the complexity of these trials.

Additionally, we want to become a leading global provider of pharmacovigilance, medical information and other post-marketing services and are looking to build additional expertise in regulatory, clinical and post-marketing services.

Ergomed will also continue to expand its co-development portfolio with a commitment to build new partnerships, and position ourselves as a leading provider of this model.

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