EPM Mar/Apr 2018 by EPM Magazine

Exploring why the US is a strong pillar of pharma manufacturing and whether the public’s perception of the industry has changed for the better or worse see pages 10-13

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Contents March/April 2018 | Volume 18 Issue 2

8 Features

Regulars 5

EDITOR’S DESK

OUTSOURCING

An update on recent Brexit developments and reactions from industry.

Here, Dale Pittock from Valley Northern explains how contract packaging can support pharmaceutical innovation.

ANALYSIS Discussing what actions are needed to support the pharma industry in its ﬁght against drug-resistant microbes.

OPINION Looking at how companies can get the best out of process research and development.

COVER FEATURE — US ROUND UP Evaluating why the US is a strong pillar of pharmaceutical manufacturing and the changing face of the country’s industry.

TECH TALK Revealing how digital technologies will herald a new era for pharma.

DIGITAL HEALTH SUPPLEMENT In this Digital Health Supplement section we address the potential of digital solutions, the challenges they pose and how pharma can ﬂourish in the transition to digital.

CONTAINMENT Describing the potential issues with containment performance testing, why split butterﬂy valves offer a costeffective solution in HPAPI containment and a new solution for moving and storing compounds that is better suited to modern manufacturing.

48 41

BIOLOGICS MANUFACTURING As the manufacture of biologics takes on increased signiﬁcance in the pharmaceutical sector, it’s clear to see why GE Healthcare’s KUBio system is growing in popularity, Lu Rahman tells us more.

PROCESS EQUIPMENT Is vacuum conveying a necessary evil or process champion? And, new developments in stopper processing equipment.

COLD CHAIN SOLUTIONS We speak with the CEO of Controlant, Gisli Herjolfsson, about the company and its cold chain solutions that are revolutionising delivery of vaccines to developing countries.

LOGISTICS A rundown of the connected warehouse and how innovations in logistics are beneﬁtting this rapidly changing world.

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editor’s desk

With recent plans announced by the UK’s prime minister to remain part of the European Medicines Agency (EMA), which would be favourable for many in the pharma industry, I will look at these developments in more detail along with the various reactions from industry.

t the beginning of March the prime minister, Theresa May, spoke about her plans to work with the European Union (EU) on terms that would mean the UK can remain part of the EMA. This announcement was met with guarded positivity from various bodies that represent the pharmaceutical and biotech industries, which have lobbied for cooperation from the initial outcome of the referendum Currently, back in 2016.

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regulatory arrangements are very complex in nature and are managed by an EU-wide system.

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“It’s good to see the PM articulating the practical dynamics of our industry of the future, when she said in her speech that ‘membership of the EMA would mean investment in new innovative medicines continuing in the UK, and it would mean these medicines getting to patients faster as ﬁrms prioritise larger markets when they start the lengthy process of seeking authorisations’,” said the UK BioIndustry Association’s (BIA’s) CEO Steve Bates.

“Every month, 45 million packs of medicines move from the UK to the EU — and 37 million come the other way,” added chief executive of the ABPI, Mike Thompson. “That is why the Prime Minister’s commitment to seek cooperation on medicines regulation would be the best outcome for patients, not just in the UK but across Europe.” Yet, the regulatory landscape is something that could be tricky to navigate. Currently, regulatory arrangements are very complex in nature and are managed by an EU-wide system. Additionally, the UK has been a major influencer within the EU system, with the Medicines and Healthcare Products Regulatory Agency (MHRA) leading at least a fifth of new medicine evaluations for the EMA and having significant input into the development of GMP and product guidance. If there are changes to these arrangements, then the supply of medicines and devices may be affected across Europe. And, that is just the start of it, according to the ABPI…

“It’s now critical that both sides prioritise patient safety in phase two of the negotiations,” Thompson added. “Delivering close cooperation on the regulation of medicines is only one part of the challenge. Making sure the supply of medicines is uninterrupted is essential to ensure patients in the UK and EU can get the medicines they need from day one of Brexit.” “By working in partnership, the EU and the UK have together achieved many research breakthroughs and developed pioneering systems of medicines regulation that have saved and improved countless lives. As the second phase of Brexit negotiations begins, it is vital that the concerns of patients are addressed with urgency,” agreed Aisling Burnand MBE, chief executive of the Association of Medical Research Charities (AMRC). “By taking healthcare and research into consideration, Brexit negotiators have the opportunity to ensure that no patient, whichever country they live in, faces unnecessary delays in accessing existing as well as new and better treatments.” Negotiations are now in full swing with a conditional transitional period softening the blow on various sectors after 19 March 2019 (the ofﬁcial date the UK is set to leave the EU), it may be that a satisfactory outcome can be reached, but the clock is ticking. As Bates concluded: “There is much work to be done but this is a positive step forward on the future of medicines regulation.” Felicity

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ANALYSIS

Ringing alarm bells There is rising tide of drug-resistant microbes that is thought of as one of the greatest threats to public health today, yet the pipeline of new antibiotics is dwindling. Here, Dr Peter Jackson, executive director of the AMR Centre, which is spearheading the UK’s response to AMR, discusses what action is needed to support the pharmaceutical industry in this fight.

or many years now, the alarm bells have been sounding on the dwindling pipeline of new antibiotic treatments. Antibiotic patent applications worldwide have dropped by over a half in the past decade and there are fewer new drugs emerging from clinical trials, with only two new molecular entities approved by US regulators between 2008 and 2012, down from 16 in the early While a new 1980s. Most worrying of army of smaller all, there have been no biotechs is new classes of antibiotics focusing on AMR introduced, effective innovation… big against the most serious pharma must be Gram-negative infections, in over 30 years.

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developers to push their innovations through testing into clinical trials. Funding initiatives such as CARB-X, ENABLE and GARD-P, have pledged around $600 million for pre-clinical to clinical translation of new treatments and diagnostics. This is a great start, but as highlighted in the recent expert report by DRIVE-AB, such PUSH funding needs to be increased signiﬁcantly to provide a sustainable earlystage pipeline of new treatments effective against AMR.

For biotechs, pharma companies and their investors, there must be progress on the market PULL side of the equation. This means ensuring that there are clear ﬁnancial rewards available to drug developers if they succeed in bringing life-saving new AMR medicines to patients.

Over the last few decades, many innovative pharmaceutical companies have pulled out of antibiotics research due to negative returns on investment in R&D and the low commercial value placed on antibiotic drugs compared to more lucrative sectors such as cardiovascular disease and cancer.

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While a new army of smaller biotechs is focusing on AMR innovation, to truly drive research forward and strengthen the dwindling global pipeline, big pharma must be encouraged to remain in — and return to — the antibiotics sector. In the past 12 months, great progress has been made in mobilising international support for so-called PUSH incentives — providing grant support to new product

But PUSH incentives are not enough to ﬁx the problem with the antibiotics market.

Progress required in market PULL

encouraged to remain in — and return to — the antibiotics sector.

Big pharma needs encouragement

and practical assistance with pre-clinical and early clinical development, leveraging the world-class R&D infrastructure at Alderley Park and across the wider support network in the UK. The Centre has announced its ﬁrst three international co-development programmes with biotech companies since opening its labs in July 2017 and has more to come in 2018.

We now need international action to establish mechanisms such as Market Entry Rewards for new drugs that might never have a commercial future, but can provide the last line of defence against the most serious resistant pathogens.

AMR Centre — key to UK efforts The AMR Centre has been established as a key part of the UK’s effort to rebuild the antibiotic pipeline by working with innovative SMEs to ensure that new drugs can be developed and brought to market as quickly and efﬁciently as possible. Alongside other sources of PUSH grants, the AMR Centre works in partnership with institutes, biotech companies and pharma to co-develop their programmes as fast as possible into patients by providing funding, expertise

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And we need healthcare payers to recognise the true value of innovative antibiotics to the healthcare system. After all, so many of today’s life-saving healthcare advances, from cancer chemotherapy to heart surgery, rely on effective antibiotics being available to prevent infections in patients. So, for the ‘biotech army’ to be truly successful, we also need to have big pharma fully on board and incentivised to provide their infrastructure and experience in bringing new antibiotics to market. That's why urgent action must be taken to ﬁx the market PULL in 2018.

COVER STORY

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OPINION

Under pressure Process R&D is vital in the development of pharmaceuticals and therapies yet more and more companies are being put under pressure to reduce time, costs and risk associated with process R&D to make treatments widely available and accessible to patients. In this article, Maria Andrielou, marketing & communication, and Thanos Andreou, scientific affairs, at VIO Chemicals, give their views on how to get the best out of process R&D.

harmaceutical process research and development (R&D) is indispensable in the development of personalised medicines and innovative treatments that deal effectively with diseases. In order to make treatments widely available and accessible to patients, the pressure to demonstrate improved outcomes at lower costs is getting Process higher. This is particularly true when Europe faces R&D in the increasing competition pharmaceutical from emerging economies, industry has such as Brazil and China.1

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a long list of criteria that must be considered.

This is where contract research and development organisations (CDMOs) can play a critical role in helping drug makers develop competitive processes without patent infringement risks and short time-to-market. But ﬁrst things ﬁrst…

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Process R&D Process R&D in the pharmaceutical industry has a long list of criteria that must be considered. These include optimal route of synthesis selection, availability of starting materials, prior art and the intellectual property landscape, quality criteria and regulatory hurdles, chemical safety concerns, toxicity and environmental sustainability, to name only a few.2 Optimal process R&D is critical as it can save signiﬁcant expenses for the pharmaceutical industry. How? By devising new concepts, employing novel methodologies and using upcoming technologies that can reduce

total chemical steps, ensure product quality and safety, guarantee consistent yields and delivery timelines, as well as reduce waste.

pathways and/or catalysts, advanced process control strategies and the implementation of new reaction and separation technologies and concepts.

Prior art route of synthesis (ROS)

Geography does matter

Designing competitive and IP-free ROSs as a way of controlling costs of materials and manufacturing is an endeavour of creativity and inventiveness. It takes meticulous work and resources to demonstrate and sustain the competitive advantage, avoid patent infringement risks and still be in line with product launch timelines.

Many CDMOs are shifting their R&D units to smaller cities where operational and workforce costs are lower, and where academic communities and high scientiﬁc output can offer fresh perspectives, stimulate new thinking and bring them closer to cutting-edge R&D solutions.

References:

Raw materials Proper selection of raw materials can have a major impact on the overall cost of the chemical process development. Whether it is about making drastic improvements in the properties of existing substances or developing new synthetic ones, optimal selection, sourcing, quality control and effective management of raw materials can lead to shorter, greener and scalable processes.

Lean manufacturing processes Designing seamless and sustainable manufacturing processes can deliver enormous beneﬁts in terms of resource efficiency, product quality and competitiveness. Improved manufacturing processes can ensure process repeatability and scalability,3 as well as generate less waste and enhance sustainability. This can be done with more efﬁcient chemical

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1. The Pharmaceutical Industry in Figures. Key Data 2017. By the European Federation of Pharmaceutical Industries and Associations (EFPIA). Sourced by the EFPIA website www.efpia.eu 2. Route Design in the 21st Century: The ICSYNTH Software Tool as an Idea Generator for Synthesis Prediction, Org. Process Res. Dev., 2015;19:357–368. 3. Strategic Innovation and Research Agenda by the European Technology Platform for Sustainable Chemistry. Sourced by the SusChem website www.suschem.org

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US ROUND UP

The changing face of pharma As pharma encounters massive shifts in public perception, which is seemingly negative in the current climate, Nick Johns, technology & digital safety investigator, ConsumerSafety.org, looks at the focus of pharma in the US and how shifting this could benefit public perception and more importantly health.

s the pharmaceutical industry has grown and evolved, its perception in the public eye has undergone a number of dramatic shifts. The massive surge in marketing1 and prescriptions of opioid pain relievers starting in the late 1990s contributed to what is now the worst public health crisis in American history,2 and much of the news surrounding big pharma today is importance of overwhelmingly negative.

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The the pharmaceutical industry’s original mission of research into new and safer solutions to a growing list of healthcare concerns is paramount, but the priorities of our current system seem to have deviated from their initial purpose.

The pharmaceutical industry has brought us some of the most impactful innovations in history, and in this climate it can be hard to distinguish it as the same industry that brought us drugs like Aspirin, Insulin and Penicillin. Problems in the system became apparent as proﬁtability became a more prominent motivator for drug research and development, but regulations are still skewed in favour of drug manufacturers.

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The FDA has developed a number of programmes over the last few decades designed to expedite the drug approval process in order to more quickly deliver promising new medications to suffering patients. The ‘fast track’ programme included in the 1997 Food and Drug Administration Modernization Act allowed qualifying drugs to shorten their development timeline by approximately one year.3 The beneﬁt of lessening the time it takes for new medications to make their way to patients is clear, but shortening the review process can potentially lead to less rigorous trials and shorter observation periods to check for possible side effects and interactions. One prominent example is Xarelto, initially considered a groundbreaking anticoagulant prescribed in order to prevent blood clots and reduce the risk of stroke or deep vein thrombosis (DVT). Praised by researchers for its effectiveness with only a single pill taken once daily, Xarelto was approved for a number of conditions and prescribed to millions. Since there is no antidote to its effects, patients taking Xarelto can experience irreversible and potentially fatal bleeding4 from small injuries that would normally clot quickly. Patients have suffered from severe internal haemorrhaging or brain bleeding, and since Xarelto does not require blood monitoring when used, it can be more difﬁcult to detect these side effects before they become problematic. Legal complaints about the drug often cite the lack of clarity around the absence of an antidote for the drug and the omission of results from some

clinical trials on its warning label, but in spite of this the drug quickly became an important aspect of Janssen Pharmaceuticals (a division of Johnson & Johnson) and Bayer revenue year after year. Accounting for over $2 billion in sales in 2016. By September 2017, reports showed Xarelto earned its manufacturer $1.8 billion in the nine months, despite so many health risks and more emerging lawsuits. As George W. Merck famously posited, medicine is for the people — not for the profits. Safely treating patients should always be at the core of any healthcare system, but recently the focus appears to be elsewhere. Lobbying in the pharmaceutical industry has been on a sharp incline. The pharmaceutical and health products industry spent a total of $78 million in lobbying in the first quarter of 2017, an increase of $10 million from the same period in 2016.5 While there is nothing inherently unlawful about lobbying, this vast spend has allowed large pharmaceutical companies to influence drug policies.6 Efforts to pass laws that would limit opioid prescribing efforts have received dramatic pushback from the drug industry. The Pain Care Forum, funded by Big Pharma, spent upwards of $740 million to curb legislation that would have put limits on opioid prescribing habits.7 The importance of the pharmaceutical industry’s original mission of research into new and safer solutions to a growing list of healthcare concerns is paramount, but the priorities of our current system seem to have deviated from their initial purpose. The current focus on speed and profitability over safety and efficacy makes it clear that regulations need to change. A shift focusing on transparency in quality testing and legislation, as well as the elimination of exploitable policies or loopholes that allow larger companies to stifle the generation of affordable generics, has the potential to not only lower our rising healthcare costs but to improve the overall quality and accessibility of medication to the public.

References: 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622774/ 2. https://www.forbes.com/sites/neilhowe/2017/11/30/americas-opioid-crisis-a-nationhooked/#2b98e9f86a57 3. https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ ucm122932.htm 4. https://www.consumersafety.org/legal/xarelto-lawsuit/ 5. https://www.opensecrets.org/news/2017/04/fewer-lobbyists-more-money-whats-going-on/ 6. https://www.publicintegrity.org/2016/09/19/20201/pro-painkiller-echo-chamber-shaped-policyamid-drug-epidemic 7. https://www.publicintegrity.org/2016/09/19/20201/pro-painkiller-echo-chamber-shaped-policyamid-drug-epidemic

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US ROUND UP

A pillar of strength Glenn Thorpe, senior vice president sales, Datwyler, looks at why the US is a strong pillar of pharmaceutical manufacturing.

he US is already a key market for pharmaceutical manufacturing, and will gain even more importance in the next ﬁve to 10 years. The largest number of biotech companies worldwide can be found in the US, investing more than $75 billion per year. Those investments are set to be growing Moving or expanding manufacturing in the US — not only due to further developments in the biotech sector, but also due to a is a current trend that shift from foreign-based to home-grown stems from different facilities and manufacturing sites.

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developments. One of the most important development is that the political landscape in the country shows a strong affinity for USmanufactured goods…

Moving or expanding manufacturing in the US is a current trend that stems from different developments. One of the most important development is that the political landscape in the country shows a strong affinity for US-manufactured goods, also in the pharmaceutical sector. As J. Miller shows in his article ‘Will Pharma Manufacturing Move Back to the US?’,1 a number of manufacturing companies already have facilities in the US. This development is particularly strong in the sector of contract manufacturing organisations (CMOs), while active pharmaceutical ingredient (API) manufacturing sites are not as present.

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One of the companies that chose the US as one of its key manufacturing sites is the Swiss-based international industrial supplier Datwyler. The company is currently building a new production facility in Middletown, Delaware, which is scheduled to start production in the second half of 2018. It will

be their second US-based operation for healthcare, but the first facility to incorporate cleanroom manufacturing in accordance with the company’s own First Line standard. Other First Line aligned facilities are based in Alken, Belgium and Pune, India. The decision for Datwyler to build a future-oriented manufacturing site in the US has, however, not been a singular, short-term decision. Opening a new facility which incorporates specific cleanroom manufacturing standards in the mid-Atlantic area of the US unifies the current trends and developments in the pharmaceutical industry: (1) the move to the US as a base for pharmaceutical manufacturing, (2) choosing the mid-Atlantic region — a pharmaceutical hotbed — as manufacturing location, and (3) the advancement of cleanroom manufacturing which also incorporates elements of digitisation. Moreover, the idea that local markets increasingly demand locally manufactured pharmaceutical components has been a driving force in the investments made by the company in the last years. That this particular trend is currently becoming strong amongst manufacturing companies shows the industrial supplier’s awareness of industry trends and developments. As CEO Torsten Maschke revealed: “As a globally acting company in the pharma industry, we need to not only observe trends but anticipate and shape them ourselves. With our new facilities in the very important markets USA and APAC, we feel we have done exactly that.” The location of the newly built facility is defined by its history as a traditional stronghold of manufacturing, particularly in the pharmaceutical sector. The mid-Atlantic region, that includes New Jersey and Delaware for example, has long been a hotbed for pharmaceutical manufacturing. This development

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is not stagnating but getting stronger. A number of international companies such as Datwyler are expanding or moving operations to states like Delaware — an important trend in today’s global economy. Companies expanding or moving to the US also provide a strong vision for the future, not only in terms of job creation but also in terms of research and progression in different industrial sectors. This is especially the case when these companies bring business to the US or futureoriented manufacturing technology that also includes aspects of digitisation and digital features. In Datwyler’s case, the First Line manufacturing standard, a cleanroom manufacturing concept. Cleanroom manufacturing will become even more important in the next few years. Whilst it is also used in other rubber and elastomer-processing industries, it is of particular importance for the pharmaceutical industry. Patient safety as one of the crucial factors for the industry, relies, to a great extent, on high-tech drug administration solutions and technologies which are produced more and more in a cleanroom The coming years environment. Certain key areas in cleanroom are bright for US manufacturing will be based pharmaceutical the focus of further manufacturing — and developments and innovations.

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new facilities, research and development will further make it an integral part of the future of global health.

Human interaction in manufacturing will be reduced to a minimum to avoid possible contamination of the product. Automation — and therefore also digitisation — will pave the way to even lower particulate levels and risk of contamination. In practice, this will be done through reducing operator handling and processing components throughout the moulding process. This will also impact the rare occurrence of component defects signiﬁcantly.

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Every step of the production process will be subject to high-tech camera inspection, from the moulding process to the washing and to the packaging of the components. The very tight acceptable quality levels (AQL) in production and the security provided by their component partner will enable any client to deliver their drugs to the patient with conﬁdence. In summary, the trends described in the above article will be leading the way towards the US consolidating their position as pillar of pharmaceutical manufacturing. Locally based research and development will do its part to underpin this position. The coming years are bright for US based pharmaceutical manufacturing — and new facilities, research and development will further make it an integral part of the future of global health.

Reference: 1. Miller, J., ‘Will Pharma Manufacturing Move Back to the US?’, Pharmaceutical Technology, 2017;41(3).

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OUTSOURCING

With a little help... In 2016, the global contract packaging market was worth $26.54 billion, and is expected to reach $47.28 billion by 2022. This compound annual growth rate (CAGR) of 10.1% is expected to be driven largely by growing demand for pharmaceutical contract packaging. Here, Dale Pittock, sales director of pharmacy packaging provider Valley Northern, explains how contract packaging can support pharmaceutical innovation.

ASDAQ’s Globe Newswire reported the predicted global growth for the contract packaging sector in April 2017. In the same article, [Global growth] and it also explained that updated other regulatory i n t e r n a tional changes like regulations that serialisation are driving were being manufacturers to introduced required outsource packaging all packaging of pharmaceuticals to contractors that to be conducted in have the relevant Class X cleanrooms. infrastructure and

expertise to ensure compliance.

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This and other regulatory changes like serialisation are driving manufacturers to outsource packaging to contractors that have the relevant infrastructure and expertise to ensure compliance. In addition, innovation in the types of medication being brought to market is facilitating packaging innovation at a rate and scale that requires costly changes to packaging lines. If drug manufacturers had to overhaul internal production lines on such a scale it would dramatically lengthen time to market, not to

mention making the cost of bringing the drug to market utterly unfeasible. By outsourcing to a specialist pharmaceutical contract packaging ﬁrm, manufacturers have access to expert support in meeting regulatory requirements and can bring their latest medical innovations to market more cost effectively.

The challenge of serialisation The threat posed by counterfeit medication has challenged the industry for years, and regulation to protect people from black market medicines has had to advance to remain effective. This is what drove the European Commission (EC) to start work to amend Directive 2001/83/ EC to address these concerns under the Falsiﬁed Medicines Directive (FMD) in 2011. The updated FMD, the ﬁnal phase of which will come into effect in February 2019, aims to protect patients by reducing the chance of counterfeit drugs entering an established supply chain. It will introduce a system to track and record legitimate medicines as they traverse from manufacturer to patient.

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Under the new directive, manufacturers will have to add safety features to every pack of medication, including a tamper-proof security seal and a barcode. The barcode will allow each pack to be serialised with an individual, random number that will be authenticated before shipping. This identifying data is going to be stored in a database managed by the European Medicines Verification Organisation (EMVO) and supported nationally by the UK Medicines Verification Organisation (UKMVO). While this tightened regulation is great for patient safety, it poses interesting challenges to pharmaceutical manufacturers. Not only is there an additional phase to add to the packaging process, which will necessitate changes to production lines, labour and machinery, there is also a dramatically increased data management burden. Businesses will need to invest in upgrading IT functionality to meet the data capture and sharing requirements of FMD. While this would be a massive capital investment for a manufacturer, if they outsource packaging to a specialised contractor already set up with local and cloud networks to support data transfer they are spared this financial hit.

Staying ahead of the curve Regulatory compliance alone seems reason enough to be driving growth of contract packaging. However, there are other beneﬁts to manufacturers choosing the right contract packer.

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An article by Doug Bartholomew on Pharmaceutical Manufacturing in September 2017 states that, “contract packagers The pharmaceutical are providing much contract packaging of the innovation sector is truly set to in how many come into its own in new drugs … are brought to market”. the next few years…

they will free up the sector to invest more funds into drug research and development and drastically reduce the time to market.

In recent years, medical technology has made some amazing advances. We have seen the development of several new drug delivery methods that are of great beneﬁt to patients, such as auto-administered biologicals and oral thin-film dissolvable medication.

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Each of these new types of drug has new packaging, labelling, storage and shipping demands. Contract packaging specialists that make sure they are cognisant of the latest drug technology developments will be able to adapt their systems, processes and production lines to easily accommodate the corresponding innovation in packaging. For example, many of these new medications rely heavily on packaging that separates required doses or equipment for different steps the patient must follow to take them safely. Additionally, this type of medication is heavily reliant on cold-chain storage and distribution. As well as new drugs, contract packagers must also be aware of any new trends being driven by pharmacies or end users. For example, the industry is currently experiencing a shift away from large count bottles for tablets and capsules. Instead, the preference is for smaller bottles or personalised medication.

However, there are a lot of plates for a packaging contractor to keep spinning to achieve this. Where possible, they need to keep things simple and hassle free. One easy way to do this is to choose suppliers that work with them in a straightforward way. At Valley Northern, for example, we provide contract packers with materials from bottles, cartons and labels through to the necessary measuring tools, gloves and disposable overshoes to keep everything running.

Keep it simple

With production often running 24 hours a day in packaging facilities, you need to know there is a reliable service to make sure you never run out of valuable supplies. We also offer our customers additional warehouse storage, so they can order cartons in bulk and simply request delivery of more whenever they need them — saving space onsite.

The pharmaceutical contract packaging sector is truly set to come into its own in the next few years. If businesses in this sector can prove the value on offer to pharmaceutical manufacturers they will free up the sector to invest more funds into drug research and development and drastically reduce the time to market.

It’s a complicated business, but there is no doubt that the pharmaceutical industry is going to become heavily reliant on outsourced packaging. Packaging ﬁrms that adapt to stay ahead of changes in the regulatory and technology landscapes will be vital in the advancement of modern medicine by solving challenges that distract drug companies from development of new treatments.

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SERIES

Time to unlock the potential Despite the ongoing trend in digital tech across the board, pharma is still lagging behind in unlocking the potential of these useful toolsâ&#x20AC;Ś

s we learned in early March from research by Accenture, there may be potentially billions of pounds that could be unlocked by pharmaceutical companies through harnessing digital technologies, yet many companies are not taking advantage of new technologies and the potential they hold.

for example, have joined forces to develop digital therapeutics for patients with multiple sclerosis (MS) and schizophrenia. This solution will be used in conjunction with medication in the treatment of patients, providing real-time patient monitoring and support through a patient facing smartphone app and clinician-facing web interface.

“Most pharmaceutical companies we work with recognise that digital technologies can drive transformation and growth, but many aren’t yet realising this potential,” said Yen-Sze Soon, managing director at Accenture.

“Psychiatric and neurodegenerative diseases place a heavy physical, mental and economic burden on patients and their families,” said Dr Jay Bradner, president of the Novartis Institutes for Biomedical Research. “With widespread adoption of digital devices, prescription digital therapeutics could potentially play an important role in future treatment models for a range of diseases with high unmet medical need.”

There are several ways that companies could employ digital technologies to transform the sector, according to the analysis from Accenture. Not only could it be used to tackle productivity challenges but it could also support patients in an integrated way through the use of wearable technologies and can back up personalised medicine through additive manufacturing, for example. Other research commissioned by DHL looking at the impact of digitalisation on the supply chain found that most companies are not fully capitalising on this revolution. This research revealed that even though many companies are testing the water with new technologies this uptake is still slow. “There is no doubt that digitalisation is having an incredible impact on supply chains and operations across the globe and is here to stay,” explained Lisa Harrington, president, lharrington group LLC, who created the report. “Companies are faced with many options as new products and applications enter the market and gain acceptance in the industry. Having a purposeful strategy for supply chain digitalisation is now essential to assess the new technological landscape and chart a way forward to reap the benefits and stay ahead of the competition.” Yet, there are some companies that are taking advantage of the potential of digital solutions. Novartis and Pear Therapeutics,

In another collaborative effort, Phillips-Medisize is working with Dance Biopharm to develop a connected version of the Dance 501 inhaler. “Advancements in drug delivery device technology have created new ways to administer drugs, thereby improving reliability and therapy adherence,” explained Bill Welch, chief technology officer, Phillips-Medisize. However, most of these companies that are making headway in the digital space all agree that it isn’t a case of simply looking at the digital transformation in a linear fashion but more as an overall approach in which each individual component is carefully thought about — in other words ‘smart’ thinking — and as ever making sure the patient and his/her experiences are thought about is vital too. “The solution is what we call Industry X.0, an action plan for embracing and profiting from technological change. More than just transforming into digital businesses, pharma companies must look at how they reinvent operating models, production and value chains,” added Soon. In the following Digital Health Supplement section we will address the potential of digital solutions, the challenges they pose and how pharma can flourish in the transition to digital.

Contents 20

THE NEXT STEP… Cognizant reveal what it will take for the UK’s life sciences to succeed in the digital space.

CONNECT THE DOTS IN DIGITAL HEALTH Medicom, a Phillips-Medisize company, looks at the swelling market of smart devices and connected health services within the pharmaceutical sector as well as how companies can use the information gleaned from smart devices to meet niche demands.

As a new era of digital drug delivery is making headway, Dr Steven Wick, 3M Drug Delivery Systems, gives us his thoughts on this digital future.

Dr Andrew Rut examines the critical role of new technology, in the form of smart pharmaceuticals and blockchain, in advancing patient autonomy and drug development.

THE FUTURE’S BRIGHT, THE FUTURE’S DIGITAL

PULLING THE RIGHT LEVERS Here, experts from Arthur D. Little introduce a framework to guide analogue-native companies in the use of levers to manage the transition to digital.

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NEW ‘TECH’ ON THE BLOCK

BETTER TOGETHER Veeva Systems discuss a new collaboration that has been formed to simplify digital engagement, which can address the growing gap between how healthcare professionals want to receive information and what can be provided.

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DIGITAL HEALTH SUPPLEMENT

The next step… According to Bhaskar Sambasivan, SVP and global markets leader, Life Sciences at Cognizant, digital systems need to evolve in order for the UK’s life sciences industry to flourish. Here, he tells us more…

ritain’s £64 billion life sciences sector is in line for a boost.1 In August, the government pledged funding to areas such as R&D, manufacturing and skills, as well as facilitating better relationships between drug companies, academia and the NHS, as part of its plan to reinvigorate its industrial strategy. Key to delivering better Funding started to trickle through for some areas in October,2 with further collaboration across life pledged in November’s sciences stakeholders will investment Budget.3

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be bringing about a digital revolution, underpinned by data sharing and analysis.

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This move has been welcomed, by industry leaders such as GlaxoSmithKline,4 which has said better collaboration is much needed if Britain is to remain an attractive location for drug makers.

Key to delivering better collaboration across life sciences stakeholders will be bringing about a digital revolution, underpinned by data sharing and analysis. In fact, over half of respondents (53%) of our recent Life Sciences Work Ahead research recognise that data mastery, in the form of big data analytics, will be critical to their digital success.5 The good news is that the report found that data is already starting to supercharge opportunity across the industry, especially with the changing nature of patient care. Smart medical devices, intelligent pill bottles, wearable bio-sensors, digestible microchips and other digitally enabled treatments, are all creating a trail of data that can be analysed for meaning and value. So how can those in the UK’s life sciences industry make sure they are fully taking advantage of new technologies and devices, as well as the explosion of data — and not simply ‘doing digital’ but ‘being digital’?

Recognise the value of digital transformation Convincing leaders on the value of digital — not just data, but cloud, mobile and social media — can often be an initial hurdle to adoption. However, in the life sciences sector, many business leaders (64%) do recognise the importance of the digital transformation journey. The biggest prize for them is the potential impact it could have on margins. The research found that by 2018, digital could help increase revenues of global life sciences businesses by 8%. This is driven by the explosion of diagnostic data flowing into and around process workflows across R&D, manufacturing and pharmaceuticals supply chain. It is clear that the future of life sciences looks very different to how it looks today. And this shift to digital could also bring about reductions in costs. By 2018, respondents expect that new digital tools and techniques will help reduce costs by just under 3%. When averaged across the surveyed companies, this comes to $974 million in savings per company.

Platforms are needed to make meaning from data However, to see these far-reaching benefits, companies will need to collect and examine data across several different processes, such as drug R&D and manufacturing, supply chain and patient care, as well

as a whole range of other sources, including sensors, wearables and apps, that will unleash even more process data. For many, this calls for strengthening master data management architectures and strategies, and having the right people to support them. They will need a platform — layers of software that gather and connect multiple data sources, and synthesise the information to create meaning from them. To unlock true business value though, this platform must become an open data exchange. This requires new relationships in the life sciences eco-system, so that data can be marshalled across the industry value-chain — from scientists, clinicians and regulators, through to pharmacists and patients — so that a whole host of industry stakeholders have the capability to index data, experiment and collaborate to improve drugs, treatments and outcomes, all the while complying with the data regulations in force.

Create a digital champion and harness new skills To make the digital switch, companies will need to choose a C-suite executive that can lead the digital initiative and ensure real and lasting change is being made. They must also invest in training to provide existing employees with new skills or hire new categories of talent. For example, data scientists and a human-centred experience designer must be part of the roadmap from day one. There should also be a big focus on creating agile software delivery and new approaches such as DevOps, which will help foster cross-departmental integration and iterative collaboration between development teams and business operations inside and outside the company. With the industry set for more government funding, but also shrouded by Brexit, the UK life sciences industry is set to undergo a massive shift — and one that is still uncertain. To ensure the country remains attractive for investors and retains its place as a leader, businesses must show that they can collaborate across the value-chain. They must create new digital eco-systems, share data where they can internally and externally, and co-invest in market developments with stakeholders. Only then will they drive true innovation and value across their own business, as well as the broader life sciences industry.

References: 1. https://uk.reuters.com/article/us-britain-eu-pharmaceuticals/uk-report-plans-boost-for-lifesciences-as-brexit-looms-idUKKCN1B92UB 2. http://www.cityam.com/274550/hammond-announces-gbp17m-boost-drug-discovery-andbolster 3. https://www.gov.uk/government/publications/autumn-budget-2017-documents/autumnbudget-2017 4. https://uk.reuters.com/article/us-britain-eu-pharmaceuticals/uk-report-plans-boost-for-lifesciences-as-brexit-looms-idUKKCN1B92UB 5. https://www.cognizant.com/whitepapers/the-work-ahead-how-data-and-digital-mastery-willusher-in-an-era-of-innovation-and-collaboration-codex2628.pdf

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15/03/2018 14:30

DIGITAL HEALTH SUPPLEMENT

Connect the dots in digital health In this feature, Medicom, a Phillips-Medisize company, looks at the potential of smart devices and connected health services within the pharmaceutical sector and how companies can use already available technologies to make the transition into connected health as smooth and beneficial as possible.

raditionally, the pharma industry has been focused on the development and manufacture of therapeutic solutions that are then prescribed by doctors without an over consideration of the patient’s experiences. The high costs associated with research and development have always put pressure on pharmaceutical companies to produce a successful formulation but in the modern day, which includes revisions to payment models, there is added pressure to attain positive patient outcomes. This more ‘patient-centric’ concept is becoming a major trend, leading the industry to look at more defined clinical and regulatory approaches, a rising proportion of biologic formulations, higher drug specificity and treatments that are linked to diagnostic data. All this comes in addition to companies delving into a sub-segmentation approach that focuses on the patient and where drugs may offer the highest benefit and efficacy. However, efficacy and safety are still at the fore when it comes to developing a drug and are essential to gain regulatory approval. Yet, for pharma companies there is more of an understanding that the journey all the way to the enduser is useful to explore in ensuring a product’s success. An understanding of this journey not only provides valuable insight into the requirements of stakeholders but also gives the company the essentials for defining services needed for patients (and stakeholders) within specific sub-segments. A good service model should be able to meet both individual and segment needs — which includes monitoring of disease specific measures, as well as adherence and compliance to treatment. In order to gain value from differentiating between the drug and service when starting the development process it is imperative that companies manage a smooth interaction with stakeholders. The shift in this balance means that bespoke connected health services will prove to be integral to getting it right.

A potential paradigm shift It is possible for connected health services to offer a paradigm shift in the pharma market as it will offer companies a direct relationship with the end user. This sort of applicability has been successful in other sectors, within which end-user ownership has led to a company becoming a market leader. However, in the pharmaceutical space there are regulatory and compliance issues which must be in control, such as safety, efficacy and pharmacovigilance, that could be a significant entry barrier. Despite these concerns, there are big companies like Google and Apple that are collaborating within the health space in order to offer a solution that serves the patient in order to influence market position. These collaborative opportunities afford companies to share the risk with the payers and means that models driven by data and finance can be employed. Additionally, through the use of smart devices companies can introduce real-world data to support approvals. This is particularly useful in situations where evidence development and conditional approval conditions are concerned and allows companies to deliver post-market data that can prove secondary measures or outcomes. So, even though doctors will still prescribe the drugs, the patient will be able to actively participate in their treatment, which can incorporate a combination of drugs, smart devices and services.

In a service-driven environment, the end-user interaction will be controlled, to some extent, by the connected health service and data flow providers, leaving the pharma companies simply as the drug supplier. However, some pharma companies may decide to absorb this service responsibility also.

Managing risk Working in an environment that is strictly controlled and regulated has left the pharmaceutical industry more concerned with challenges rather than opportunities that can arise out of new technological services, such as connected health. Those concerns that are considered to be the most important include security and data privacy — which although vital are also controllable. After the advent of smartphones, which enable people to stay connected easily, many companies across a breadth of industries have taken advantage of this connectivity to gain insight and knowledge into consumer behaviour. There is the potential for pharmaceutical companies to utilise this connectivity to fulfil patient-centricity claims, so long as the risks are managed appropriately. Furthermore, smartphones and related devices can also offer patients independence in their own care journey, which is becoming more attractive and desirable for them in the modern day. In order to be successful in the delivery of a system, companies must factor in some key strategic considerations and basic rules. At the base of it all is gaining an understanding of the needs and challenges of specific stakeholders in relation to disease management. By identifying these initially, a company can then visualise the potential value drivers for the service. This process should be done on an individual basis in a specific disease and care-journey context. This individualised approach means that when designing and developing a smart device and connected health solution flexibility and options that are unique to the user are imperative so that patients are engaged. For example, the first fully connected solution that is available in the market from Bayer — the BETACONNECT electronic autoinjector and its associated myBETAapp regulated connected health platform — has undergone regulatory assessment for each aspect, device, service combination and product set-up, before being granted approval. This device and platform supports multiple sclerosis patients and their respective healthcare providers through the full care journey.

Time and cost implications Meeting specific needs of the patients, which is the aim of smart devices and connected health solutions, does not necessarily mean that time to market will be dramatically increased compared with that of an ‘offthe-shelf’ technology. Using core technologies that have already been tried and tested in other devices is useful for companies as a starting point in the development of more specific and bespoke solutions. Development of these should then be possible in a similar timeframe to ‘off-the-shelf’ solutions but also enable companies to deliver solutions that are specific to stakeholders needs, such as connected health options.

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It is also possible, through incorporating the underlying hardware, security, integration interfaces and analytics into the standardised platform, to roll-out connected health solutions before launching a device. An added benefit of this can be improving the value of the solution as it is possible to offer early interaction with stakeholders. The software and app-interface development elements of a connected health solution usually deal with the drug and disease specific portions. These should only require a short lead time of around 12–18 months. It is inevitable that there will be more costs associated with connected health services and smart devices, but these can be counter-balanced when considering the significant value gained from the stronger market position and longer-term relationships with stakeholders that is possible through these bespoke offerings. Therefore, companies should consider the move into this market as a transformative opportunity. This opportunity means that companies should concentrate on how it can add value from different parameters in addition to the drug itself. In combining these different parameters on top of the ‘pure’ treatment — a preventative care model — will mean that market opportunities are made broader for companies and connected health can prove a differentiator. However, it is important for pharmaceutical companies to clearly see this future as an opportunity to not only be a provider of drugs but also a provider of solutions to total disease management.

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It is possible for connected health services to offer a paradigm shift in the pharma market

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Industry influencer As is the case in other industries, user focus is becoming of greater importance within the pharmaceutical sector. A greater requirement for solutions to be patient-centric and alternative payment schemes are trending and changing the way in which companies should address the development and design of disease solutions. In this vein, it is obvious that connected health services and smart devices will play an integral role in influencing the industry. There are already some technologies and solutions available allowing the stakeholders to be more independent and have more interaction throughout their care journey. With more technologies and solutions being launched it is important that companies realise the value of these services and start to implement them into their future development plans. However, these changes do not necessarily mean that companies need to ‘reinvent the wheel’ instead smart thinking can enable companies to adapt by using existing, proven technologies that reduce the risk associated with developing a connected service while still adding value and being competitive with ‘off-the-shelf’ solutions.

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The future’s the future’s

DIGITAL HEALTH SUPPLEMENT

As a new era of digital drug delivery is making vice president, Product Development & Commer Delivery Systems, gives us his thoughts on this d

cross the drug delivery industry, there is currently a big movement toward digital enhancement of inhalation devices used by patients with asthma and COPD. With fewer step-change improvements in drug therapies, the pharmaceutical industry is now focusing its attention on drug delivery technologies as a means to improve compliance and therefore patient outcomes. The concept of digital health will allow us to properly equip patients to manage their condition and ultimately take control of their health.

A patient-centred model A focal point of my career in pharmaceutical research and product development has been to drive innovation with a priority placed on improving patient outcomes. The technological advances that have made digital health possible are changing the landscape of device design to a more patient-centric model. Traditionally, drug delivery methods were designed without much consideration for the patient experience. Now, product developers and engineers are considering the challenges facing patients first. They use these insights to improve drug delivery device design, and by addressing patient challenges directly, they improve patient outcomes in the process. A 2008 research report showed that up to 94% of patients make mistakes when using their inhalers, and these were the dry powder inhalers that were intended to be easier to use.1 None of the current devices are perfect, with up to 76% of patients struggling to use metered dose inhalers as well.1 Also, patients struggle to adhere to their medication schedule. When patients forget to dose themselves or inadvertently use their inhalation devices incorrectly, it doesn’t matter how great the drug is — it will be less effective. Digital health is helping to solve these usability and adherence issues. For example, the 3M Intelligent Control Inhaler (ICI) is breath-actuated so that patients do not have to coordinate their in-breath with triggering of the device, and actuation is triggered at a low flow-rate and at the optimal point within the patient’s inspiration cycle, so that even patients with a severe condition and poor lung function can use the device. Proprietary flow-sensing technology optimises the inhalation cycle and can detect whether a patient is inhaling the drug properly to ensure a full dose is received. The device can connect to a smartphone or tablet for reminders and further instructions, and it can record data for sharing with a healthcare provider, to influence and inform healthcare decisions.

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e’s bright, e’s digital

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The technological advances that have made digital health possible are changing the landscape of device design to a more patient-centric model.

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y is making headway, Dr Steven Wick, & Commercialisation, 3M Drug hts on this digital future.

The focus of our efforts is to identify areas where drug delivery device technologies could add significant benefits to the patient and help manage costs for the provider and payer. In that vein, 3M has also developed a respiratory tracker to help patients identify and monitor triggers that result in breathing difficulty. The 3M Respiratory Tracker is not a drug delivery device but a consumer wearable designed to give the wearer a greater understanding of how their breathing patterns are related to environmental or weather-related considerations. It provides personalised forecasts tailored to an individual’s potential triggers in their local environment, while delivering dynamic tips and insights relating to breathing and activity.

Bringing the vision to life One major factor that stands in the way of future advancements in the digital drug delivery space is cost. Billions of dollars per year are invested in digital health start-ups, and creative solutions are always on the horizon. However, these innovative inventions are struggling to move from the development lab to the pharmacy counter because we have yet to generate the pharmaco-economic models and the associated business cases required to create the necessity for these new digital drug delivery technologies. To move forward, it is important for all parties involved: pharmaceutical companies, payers, providers, and patients, to understand how total healthcare costs will benefit from these new technologies. If a patient is receiving the right dose of medication at the right time on a consistent basis, one could surmise that the patient’s symptoms would be better managed and the patient would make fewer trips to the doctor’s office or emergency room. In the end, this will drive down overall patient costs and significantly reduce the financial burden on the healthcare system. We must also consider the investment of time. For healthcare providers, helping patients is the ultimate goal. However, it’s typically the provider’s responsibility to teach his or her patient how to properly use the device, which means the provider must first be trained in how to use it. At 3M, we are sensitive to these factors and keep input from patients and providers at the forefront of all development stages. Our goal is a product that is as straightforward and beneficial as possible for both parties. Despite the bells and whistles that new technology allows, an inhalation device must be intuitive to use — plain and simple.

Moving forward To stay aligned with this new era of drug delivery, organisations across the board have had to adapt. Here at 3M, we must now be more strategic in our R&D efforts than ever before. Because of the unique financial framework outlined above, we can no longer afford to innovate simply for the sake of innovation. Instead, we start by identifying a problem and then search for a feasible solution. It is an exciting time to be involved in the drug delivery industry. I believe going digital will improve consistency in drug delivery, increase the efficacy of drug products, and reduce the opportunity for patient errors. I also believe it will offer providers and payers valuable new data to help them identify patients who need extra intervention, thus preventing a potentially catastrophic and costly event. Everything you can imagine doing, there is a possibility with digital health, which is why it will continue to be an unstoppable transition in the inhalation therapy for years to come. Reference: 1. Lavorini et al., Respir. Med., 2008;102(4):593–604.

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One major factor that stands in the way of future advancements in the digital drug delivery space is cost.

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There is a clear set of initial steps an established, analogue-native medical technology organisation should take to get started on a digital transformation.

DIGITAL HEALTH SUPPLEMENT

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Pulling the right levers In this article, Mitch Beaumont, Prashanth Prasad, Ulrica Sehlstedt and Mandeep Dhillon, Arthur D. Little, introduce a framework to guide analogue-native companies in the use of levers to manage the transition to digital.

stablished medical technology and pharmaceutical companies as well as new entrants to the medical technology sector can beneﬁt from offering digital products and services. But for existing companies, whose development models are built around compliance with regulations, moving to digital is typically a difﬁcult prospect. We have created a set of ‘levers’ that executives can consider in order to proactively manage the changes necessary for digital transformation.

Navigating the new opportunities Recent advances in technology, along with changes in healthcare reimbursement models and care delivery pathways, have created opportunities for digital products and services to play an important role in healthcare. The beneﬁts of digital, such as lowering costs, increasing patient engagement and improving outcomes, have been discussed extensively.1 Many new entrants and start-ups are taking advantage of the opportunity and challenging established healthcare companies, hoping to get a share of an industry that makes up about 10% of the global economy.2 These organisations employ newer, more agile working models that are better aligned with being digital. A further advantage is emerging: regulators that have not been friendly to software products in the past have started to embrace new iterative development approaches to accommodate the growth of digital health.3 In contrast, established medical technology companies (or medtech divisions within pharma companies) face a different picture. Their operational and cultural DNA has been steeped in rigid company processes that were created to minimise the risk of non-compliance with regulatory requirements such as FDA guidance. For many of them, results have been elusive as going digital has strained their current ways of

doing business. In fact, being successful with digital products and services requires established companies to rethink their business models and the underlying operational models. This can be seen with a recent example of an established medical technology company that has found success.

Roche Diagnostics: a more holistic approach Roche Diagnostics saw insufﬁcient outcomes from diabetes treatments, and decided a more holistic approach was needed to manage diabetes. To that end, it adopted an ecosystem approach to connect and offer integrated digital solutions to all stakeholders involved in the diabetes management cycle, in order to optimise care processes and improve prevention. Before the ecosystem was created, Roche’s main value proposition was offering its diabetes management systems, such as glucose meters and insulin pumps. With the ecosystem, Roche could expand its value proposition for patients and enable ‘more time in range’, leading to fewer hospitalisations. Roche became a partner to patients, helping them manage their conditions, rather than just being a manufacturer of products. Operationally, Roche separated Roche Diabetes Care into a subsidiary with its own operating model to facilitate the creation of a world-leading big-data ecosystem for diabetes management. A new, global hub with the required digital and IT capabilities was created in Barcelona, and co-promotion and distribution partnerships were set up with a number of complementary companies, including Medtronic, mySugr and Senseonics. With this successful digital transformation, Roche went from only treating sick people in acute care settings to enabling treatment in chronic care and remote settings. In addition, it increased patient engagement to proactively assist in prevention by improving patient lifestyles.

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‘Pulling’ the best ‘levers’ to effect change Based on our experience, and from assessing examples such as Roche, we have identiﬁed two sets of primary levers that executives can use to impact the changes to their companies’ business and operational models that are necessary to support a digital business. The speciﬁc levers used, and the degree to which they are ‘pulled’, will be

unique to each company’s environment and its ultimate goals for digital. Most medical technology companies, including the examples cited above, will focus more on two or three of these levers, with minor changes in the others.

Business model levers • Value proposition. Digital products and services can enhance or shift a medical technology company’s value proposition in the market. For example, it can extend its products to provide remote-monitoring capabilities that improve care and reduce costs. Or it can offer tools such as applications and reminders to increase patient engagement and improve adherence. Typically, a digital business will want to build upon the company’s existing core value proposition, rather than creating a completely new one.

• Value extraction. Most medical technology companies have focused on selling devices, or generating revenue per unit. However, monetisation of value can take on alternative forms with digital, such as serviceoriented models (e.g., selling hours of operation for a home health device versus the device itself) and datacentric models (e.g., selling the data generated by the devices). These new models may require working with government payers and insurance companies to gain support for reimbursement.

• Markets served. Digital can enable a company to shift or expand the markets it serves to open up new business opportunities. For example, digitally enabled products and services can be marketed to caregivers of the elderly or children who are willing to pay for access to data on activity or medication adherence to give them peace of mind. Alternatively, companies may be able to create new business relationships with other value-chain players, such as home health companies, by providing information that improves the effectiveness and efﬁciency of in-home care delivery.

Operating model levers • Process/methods. Going digital requires new ways of working. Software development cycle times are faster, and will be more effectively enabled by agile methods, which are fundamentally different from existing linear or phasegate approaches employed by most medical technology companies. Robust technology and portfolio management methods are needed to keep up with the faster pace of technology change and ensure R&D resources are invested in the right areas. • Delivery network. Becoming digital can create opportunities for medical technology companies to engage with a broader ecosystem to develop offers and reach the market. The complexity and system-like nature of many digitalcentric solutions creates attractive opportunities to engage development and/or delivery partners. • Capabilities/footprint. Adding digital elements to a portfolio will require new capabilities in areas such as application development, data management and security. In addition, medical technology companies will require capabilities in areas such as consumer insight and behavioural economics to ensure their digital-health solutions meet patient/ user needs and expectations. The organisational footprint should also be an important consideration to help gain technical talent or local market knowledge and access. These levers are depicted in the framework shown in Figure 1, where a more signiﬁcant change in each group of levers collectively creates an overall more signiﬁcant change along the respective dimension. Companies can use this visualisation to qualitatively assess the degree of change — and change management — they will need to make to support a digital strategy and transformation.

Beginning steps There is a clear set of initial steps an established, analogue-native medical technology organisation should take to get started on a digital transformation. (See Figure 2.) Even if an organisation has jumped into creating digital elements or dabbled in deploying a digital service, ivt will pay dividends to go through the steps to ensure there is a strategic alignment between what the market needs and what the company does.

STEP ONE

STEP THREE

Get a firm understanding of stakeholder needs, especially latent needs, of patients, care givers, providers, and other relevant players independent of the application of digital.

Evaluate the implications to the business model and underlying operating models for each prioritised solution concept.

STEP TWO Develop ideas into solution concepts, often with multiple ideas brought together into one.

STEP FOUR Only once the implications for the business model and operating model are understood can an organisation set its strategy and plan for going digital.

Conclusion There is significant value to be captured with digital products and services in the healthcare industry. Many new entrants are well positioned to compete because their models are oriented towards software development — more so than existing, analogue-native

medical technology companies, which are organised to comply with regulations. For these companies, going digital will require significant business- and operational-model changes. Conclusion

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References: 1. Succeeding with Digital Health – Winning offerings and digital transformation, Arthur D. Little, March 2016 2. In the US, the world’s largest economy, health expenditure is over 17% of GDP. Source: World Bank Data (data.worldbank.org) 3. As an example, see the US FDA’s Digital Health Software Precertification (PreCert) Program at www.fda.gov

DIGITAL HEALTH SUPPLEMENT

New ‘tech’ on the block Dr Andrew Rut, CEO and founder of MyMeds&Me, examines the critical role of new technology, in the form of smart pharmaceuticals and blockchain, in advancing patient autonomy and drug development.

The advent of smart pharmaceuticals has substantially changed the way in which the pharmaceutical industry interacts with its patients. It is now possible to collect purer data faster, facilitating patients’ autonomy over their own health, and making the research and development (R&D) process more efficient for drug developers. While some argue that greater patient autonomy may lead to increased data variability, the volume of data that can now be collected means that these anomalies can be quickly identified and addressed. Ultimately, purer data, collected at source and in greater quantities thanks to increased patient engagement, facilitates the advancement of pharmaceuticals whether traditional or ‘smart’ and therefore drives improved patient outcomes.

Digital empowerment Patients empowered through digitalisation have provided pharma companies with the opportunity to collect significant quantities of real-world data previously unavailable to researchers. This is leading to increased insights across the R&D lifecycle as it is now possible to collect vast quantities of complete data, thus rapidly improving the drug development process. Digital data can be collected from the patient directly via wearable technology making its collection much more efficient and enabling clinical trials to be carried out remotely. According to a 2016 study by Frost & Sullivan, a market research company, the US remote patient monitoring market is expected to reach a compound annual growth of 13.2% through 2020. Remote monitoring allows researchers to have access to data earlier in the drug development process, which in turn enables them to react more quickly to safety issues. This data can then be leveraged by the industry to develop medicines that optimise the benefit-risk profile for individual patients. Providing patients with greater autonomy has also facilitated patient compliance with medicines. Self-monitoring has been proven to encourage drug adherence amongst patients, as shown by a 2017 study by Dr Lilla Náfrádi, researcher at the University of Lugano. Smart pills or Ingestible Event Markers (IEM), which have recently been approved by the FDA, help patients to feel empowered with regards to their own health, as well as informing R&D professionals with the data they need to reassess a treatment plan if necessary. The pill includes an embedded sensor that digitally tracks if patients have ingested it, offering a unique benefit for patient groups with typically low adherence. Thanks to their tracking capability, smart pills help patients adhere to their medicine while simultaneously alerting their care team of gaps in the regimen. The goal is to provide early intervention and support for those patients at risk of disease relapse through non-adherence. With great power comes great responsibility Although increased patient autonomy has resulted in the collection of vast quantities of data, it has also increased the potential for data inaccuracies, which, if not identified and addressed, could impact upon drug safety and efficacy. Data accuracy

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is critical for the advancement of smart pharma. One of the greatest challenges facing R&D teams throughout the pharmaceutical industry is having data that is consistent and reliable. The ability to manage and integrate data from source to drug utilisation is fundamental in the pharma advancements. As critical gaps in information cannot be corrected post processing, relevant and accurate information must be collected at source. Missing this opportunity means that access to valuable information may be missed for good. Volumes of data create challenges of downstream processing and analytics. Responding to this the pharmacovigilance industry is beginning to apply artificial intelligence (AI), which makes it possible to sift, structure and collate data across internet sources, reducing manual effort through application of preloaded algorithms which can decipher human semantics. Clearly such algorithms have to be transparent and subject to human scrutiny to ensure they are operating appropriately and that the precision/recall of the AI

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Although the pharmaceutical industry has advanced patient autonomy over the last couple of decades, smart pharmaceuticals are still very much in their infancy.

engines is at a level that provides meaningful outputs. Increased patient autonomy necessarily raises questions about patient confidentiality. Greater transparency and the sharing of patient data for further scientific research is an increasingly important issue for those conducting clinical trials, as well as for patients participating in the studies. A conflict remains between

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the appropriate sharing of clinical trial data for R&D, and the maintaining of patient confidentiality. The introduction of General Data Protection Regulation (GDPR) in 2018 is challenging some of the existing processes and in particular the secondary use of data, so the pharmaceutical industry must proceed with diligence and ensure consent to use patient information is obtained. New technologies such as the blockchain — a decentralised data management system utilised for its security, transparency and traceability — are likely to become more commonplace in clinical trials. When applied to clinical trials, the blockchain can ensure authenticity and traceability of patient consent. The proof of consent can be timestamped and stored on the blockchain, notifying patients of any change in procedure requiring them to renew their consent for the sharing of their information. Most importantly, data can be encrypted via the blockchain, ensuring that a patient’s identifiable data cannot be revealed. Although still in the early stages of its development, the use of this technology in the pharmaceutical industry has the potential to have a significant impact on data security.1–3

Still in its infancy Although the pharmaceutical industry has advanced patient autonomy over the last couple of decades, smart pharmaceuticals are still very much in their infancy. New technologies such as the blockchain will allow for transparency in the sharing of information while maintaining the highest levels of privacy. As increasing numbers of patients collect their own data, it is likely that the manufacturers of these technologies, such as wearable devices will move from supplying the industry, to sharing aggregated data directly with the patients. References:

While very attractive in the post-approval setting, how patient feedback is managed

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676196/

during drug development will have to be considered carefully to avoid bias and

2. https://insights.dice.com/2017/12/28/how-a-i-blockchain-big-data-reduce-costdrug-making/

changing outcomes. As the trend for patient autonomy progresses, patients will

3. https://theconversation.com/could-the-blockchain-be-the-salvation-of-thepharmaceutical-industry-88429

become increasingly well informed and the collection of efficient, accurate and secure data, and its application to R&D, will become increasingly important.

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DIGITAL HEALTH SUPPLEMENT

Better together To address the growing gap between how healthcare professionals want to receive information and what can be provided, the world’s largest pharma companies have collaborated to simplify digital engagement. Jan van den Burg, vice president, commercial strategy, Europe, Veeva Systems tells us more…

oday, there are greater expectations among healthcare professionals (HCPs) for digital engagement with life sciences companies. However, despite the rise of digital in life sciences, the ability for organisations to provide the right information to doctors quickly and effectively remains a challenge. Part of issue lies in the complex and siloed processes for educating and informing doctors that exist between commercial and medical organisations. But the problem is compounded by the fact that each life sciences company provides digital information differently, across many portals and channels. For HCPs, this creates a significant burden as they simply do not have the time to wade through a sea of websites and portals to get critical product information. And it is this friction that consequently lowers HCP consumption of digital information from life sciences companies.

There is a growing gap between how HCPs wish to be served information and what the industry can currently provide. There is a higher expectation among HCPs for data to be at their fingertips. In fact, studies have shown that when doctors need information about a medication, they often go to Google, Wikipedia, or other second-hand sources before turning to the actual life sciences company responsible for creating the product. In fact, one study indicates that Wikipedia has become a top medical information site, with up to 50% of HCPs The goal of Align using it to educate themselves about medical conditions or treatments.1 Biopharma is to make

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it faster and easier for HCPs to connect with life sciences companies with universal technology standards that will simplify access to information.

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To address this growing challenge, the world’s largest pharmaceutical companies have come together to form an industry-standards group called Align Biopharma. The goal of Align Biopharma is to make it faster and easier for HCPs to connect with life sciences companies with universal technology standards that will simplify access to information. Ultimately, the patient benefits.

“Our goal is to improve the overall customer experience for healthcare providers,” said Scott Cenci, vice president of global therapeutic operations IT at Biogen, one of Align Biopharma’s founding members. Other founding members include Allergan, AstraZeneca, Biogen, GlaxoSmithKline, Novartis, and Pfizer. “We are partnering with this group to architect industry standards, which will help us to achieve that vision,” added Cenci. Align Biopharma will define standards that are open and global to streamline digital interactions with HCPs. Initially, the group is focusing on two new standards to facilitate seamless digital engagement and simplify the HCP experience: identity management and consent and communication preferences.

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Streamlining identity management

Industry collaborations picking up steam

Life sciences companies maintain rigorous registration processes for access to branded sites and portals. As such, a physician may need a dozen different registration identifiers (IDs) with a single company. As the number of sites, portals, webinars and other channels grows, so does the number of access points, making it acutely difficult for providers to quickly access what they need. Multiply this across all the various drug manufacturers with which an HCP engages, and the problem grows from a minor inconvenience to a significant burden.

Collaboration in the life sciences industry is not new. TransCelerate Biopharma and the Clinical Data Interchange Standards Consortium (CDISC) are examples of successful industry collaborations in clinical. Align Biopharma is the sign of a new, industry-wide priority to improve the HCP experience by tackling long-standing challenges in the commercialisation of drugs and treatments and also how HCPs As digital transformation engage with life sciences companies. charges forward in Companies are coming together to solve life sciences, common these challenges because they recognise standards are key to that the industry has a common goal to make things easier for their shared removing some of the customers. current roadblocks

“It’s difficult keeping track of all the username and password combinations required to access information from biopharma companies,” said Dr David S. Wernsing, FACS, bariatric surgeon at Penn Medicine. “Having a fast and convenient way to log into various digital sites and applications will dramatically simplify how I connect with the life sciences industry and deliver care to patients.” A standardised process to deliver the right information to common customers will remove current roadblocks for HCPs. To start, Align Biopharma recently finalised and introduced an identification and authentication standard to enable single sign-on for HCPs to access online content through many different channels across companies. This new standard will improve how life sciences companies interact with their customers, and help to streamline HCP access to the drug and treatment information required to facilitate patient engagement. The identification and authentication standard represents a major step forward for the life sciences industry, and a watershed moment for collaboration. It will allow biopharma and technology companies to align around a common way to provide HCPs with easy access to online content, and validate that the right licensed provider is getting what he or she needs quickly. Put simply, it will replace dozens of passwords with only one. “The industry, working together, can harmonise digital engagement and information access and create a better experience for our shared customers,” explained Patrick Retif, vice president of IT, Global Commercial at Allergan.

Managing consent and communication preferences Due to industry regulations, managing consent and preferences can be one of the most difficult aspects of digital communication with HCPs. The European General Data Protection Regulation (GDPR) comes into effect on 25 May, requiring all companies doing business in Europe to develop compliant models for data consent, collection, storage and processing. While the regulation will have a significant impact on organisations in all industry sectors, it will have unique compliance challenges for global life sciences organisation.

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and paving the way for

“Technology standards will solve a significant business problem across companies to leverage the industry by helping get information the potential of digital to stakeholders when and where they technologies to reach need it,” said Ed Kloskowski, VP, head of commercial IT at Shire. “At Shire, we more HCPs. are focused on meeting the needs of underserved patient communities. Joining forces in Align Biopharma to work together to harmonise digital engagement in a way that will ultimately help patients is one more path to serving our patient community.” Initially formed with six founding companies, Align Biopharma membership currently stands at 23, including 14 leading biopharma companies, plus technology and service providers. Regardless whether a company is an Align Biopharma member, everyone will have access to standards published by the group.

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“Align Biopharma represents the industry coming together to put the customer first and transform the HCP experience,” said Henry Levy, president of Align Biopharma. “With our first standard now available, our goal is to deepen collaboration to build technology solutions and encourage their broad adoption in life sciences so we can better connect companies and HCPs.” As digital transformation charges forward in life sciences, common standards are key to removing some of the current roadblocks and paving the way for companies to leverage the potential of digital technologies to reach more HCPs.

Reference: 1. https://www.theatlantic.com/health/archive/2014/03/doctors-1-source-for-healthcareinformation-wikipedia/284206/

A forthcoming standard from Align Biopharma will create a common definition for consent and preference management, and help drive consistency in how HCPs specify communication preferences with each life sciences company. This will also provide clarity for HCPs to opt into or out of receiving information, so HCPs can get the information they need, how they want it. For example, one HCP may want to receive information via email from a life sciences company, but not a phone call. Align Biopharma will greatly simplify this.

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CONTAINMENT

Tried & tested? In this article, Michael Avraam, global product manager at ChargePoint Technology discusses the potential issues with containment performance testing, the data collection methods and how the results are interpreted, as well as the impact this may have on the end user. He also describes some techniques and developments that may help to ensure efficient containment performance testing.

rowing demand for high potency active pharmaceutical ingredients (HPAPI) and the rising prevalence of speciﬁc therapy areas, such as oncology, immune-suppressants and hormone, are fuelling the As the use of high potency need for high potency handling capabilities. As containment systems is rising, the use of high potency manufacturers are looking at more containment systems is innovative containment strategies rising, manufacturers are and containment verification has looking at more innovative never been so important. containment strategies and containment verification has never been so important. However, it’s critical to understand the variations in testing and the challenges posed by potential differences in the interpretation of results.

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Industry and regulatory outlook As the biopharma market is continuously expanding, including global demand and growth in the oncology market, there is growing need for the development of potent compounds and an increase in conventional drug manufacturing using HPAPIs. By the end of 2024, the cancer segment is projected to reach close to $100 billion in value, expanding at a CAGR of 6.5%.

Indeed, the containment solution market is expected to grow rapidly by 2020 and with this increasing need for high potency handling capabilities, more advanced control strategies in HPAPIs are vital to both the quality of ﬁnal products and critically operator safety. We have already witnessed the market diversify with technologies such as isolators, restricted access barrier systems (RABS) and split butterﬂy valves (SBVs) now in use to safeguard drug products and operators throughout the manufacturing process. Closed transfers, such as the use of SBV, are growing in popularity as they limit manual intervention, reducing the risk of cross contamination and limiting the presence of airborne dust particulate to meet operator safety targets.

ISPE SMEPAC guideline The increase in drug manufacturing using HPAPIs means that pharmaceutical manufacturers are having to invest in high potency facilities and equipment to deal with the associated risks, and these have to be implemented and validated. For example, before a manufacturer can implement a new control device within its process, it should be assessed in line with the International Society for Pharmaceutical Engineering’s (ISPE) Standardised Measurement of Equipment Particulate Airborne Concentration (SMEPAC) guideline for its particulate containment performance. This is a guide to demonstrate how the containment device will perform as part of a laboratory condition test, not in a particular process in a real-world manufacturing environment. ‘The guide aims to define current good practices providing information to allow organisations to benchmark their practices and improve on them. Specifically, the guide provides a methodology to derive data associated with handling of pharmaceutical ingredients that is useful in the assessment of potential risks.’ In the late 1990s, occupational health professionals focused on worker exposure measurement as the primary target to qualify containment equipment through workflow outcomes, regardless of the source. The method was formalised as SMEPAC, later adopted and revised by the ISPE. While widely welcomed by the industry, the random nature of this guidance on sampling methods and distribution makes it challenging to achieve a specific measure of containment for equipment or devices. The data lacks statistical validity and more importantly, the method would be better suited if it provided a baseline dataset for future integrity testing.1

Figure 1: Global HPAPI market by therapy.

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Key considerations

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There are many factors that can affect the interpretation of the SMEPAC test results, including the testing protocols, the placebo, test equipment and the data analysis.

The testing protocols detailed by SMEPAC allow for a certain amount of inconsistency. For example, referring to transfer quantity, the SMEPAC guideline notes ‘the masses are intended to fully coat the exposed seal and operating surfaces and are suggestions’. For example, as there is a suggested weight range documented within the guide, expecting consistency in results between devices tested with volume variation will no doubt result in inconsistent results.

There are various types, particle sizes and levels of detection of placebos that the SMEPAC guide recommends during validation testing, for example, lactose, paracetamol, mannitol and naproxen, but how relevant is the test placebo to the real-life API eventually to be used and has each supplier tested with the same placebo? These are two questions that could affect the interpretation of the results. Equally, there is the potential for some considerable differences from various samplers when using the same test — it is possible for test equipment with the same performance to show differing results.

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DIAMETER

MASS

0 to 100mm

0.5kg or more

100mm to 200mm

5kg or more

200mm or more

25kg or more

Figure 2: Test material mass to be used for each test cycle (example test table).

Within the industry, manufacturers often look at the data following this laboratory test and use it to qualify the selection of the required containment technology for their process. However, comparing these tests like for like could prove to misrepresent reality. There are variations in the way the containment performance tests are performed and the interpretation and utilisation of the results obtained can be inconsistent, so there is a risk to presume that performance should be the same, whether it’s in the laboratory or the manufacturing environment. But should it? In a risk based era, we need to consider the areas of variability and how these could eventually lead to issues, if not addressed.

Application and usage Ensuring operator safety and reducing levels of contamination is essential during high potency manufacturing. As human intervention is present at almost every stage of pharmaceutical manufacturing processes, solutions to counter the potential risks are vital. This needs to be achieved in a manner that does not impede on productivity and operability, therefore identifying an appropriate solution can be a challenge. Validation testing also needs to reﬂect operator intervention to ensure that the containment device, some of which can be reliant on operator technique to achieve performance, is tested accordingly. The containment should also be validated at each step where potential exposure is present in its normal environment, including full risk assessment for the whole process. For example, a charging application that has not undergone contained dispensing operation prior to being within the laboratory environment, cannot be compared measurably to its normal application within the manufacturing environment.

damage, before it is used, introduces further risk. Frequent monitoring and preventative maintenance helps to safeguard the reliability of the containment solution. By limiting manual intervention, this will also help to maintain a like for like result.

Using technology to address containment requirements New design technologies such as SBVs have evolved over the last 25 years to address the more stringent containment demands when handling potent compounds and remove the risk of airborne exposure. These valves can be integrated with other containment solutions such as isolators to enable the transfer of potent compounds and are used in many applications when not only dust control and containment is a concern but where product ﬂow, yield and sterility are also important. It has been a common perception that containment performance is directly associated with the levels of particulate residue visible after separation of the containment device, but performance tests have proven that the containment performance is not directly linked to the level of visible residue. Nonetheless developments in extraction methods have led to the recovery of potentially airborne particulates, thereby reducing and eliminating these visible particles. Extraction offers an excellent, robust solution to achieving repeatable By removing the risk performance. from human intervention, Other ways of helping to improve valve performance include double gloving, enhanced wiping procedures and waste disposal. However, by further reducing human intervention with an automated approach, may it offer an alternative option for reducing risks further?

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[wireless monitoring] technologies will add a new dimension to traditional containment strategies to allow manufacturers to meet the most stringent regulatory requirements.

As the industry is moving in this direction, by incorporating wireless monitoring technology, it will be possible to receive vital equipment performance data and generate an audit trail; allowing maintenance, health and safety and compliance teams to make informed decisions to proactively manage their maintenance and validation programmes. By removing the risk from human intervention, such technologies will add a new dimension to traditional containment strategies to allow manufacturers to meet the most stringent regulatory requirements. With the potential to enhance performance validation monitoring they also provide a real-time, ‘real-world’ method of validating and conﬁrming equipment performance in situ.

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Conclusion There are several considerations when containment testing. Due to the clear differences between laboratory and manufacturing environments, it is important to understand the potential limitations of the SMEPAC guideline, which is based on a laboratory test. As the industry continues to move forward with technological advancements to capture more repeatable and reliable date, there is an opportunity to improve the levels of containment performance and validation testing to maybe eventually replace the single laboratory test.

Reference:

Questions should also be considered around preventative maintenance. The condition of the device and the identiﬁcation and rectiﬁcation of any

1. http://www.pharmtech.com/environmental-containment-performance-there-accountability

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COVER STORY

Isolator Technology?

Identification Advice Implementation

Your Process Under High Containment

Seeking advice on how to improve your manufacturing strategy? Visit us Interphex, New York, 17 – 19 April, booth 2471 Making Pharmaceuticals, Coventry, UK 24 – 25 April, booth 241

36 www.dec-group.net

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Powder Handling Excellence

The butterfly effect

CONTAINMENT

More and more newer drugs contain high potency active pharmaceutical ingredients (APIs), which require careful handling and specialised equipment. Here, Precision Polymer Engineering (PPE) highlights why split butterfly valves offer a cost-effective solution and offer insight into the best sealing material for containment processes. High containment valves: High potency sealing in pharmaceuticals A signiﬁcant proportion of new drugs under development contain high-potency active pharmaceutical ingredients (APIs), leading to explosive growth in demand for their production. However, the cytotoxicity of APIs presents a number of challenges, including handling of said ingredients, and the required investment in specialised containment to ensure that employees and their working environment are protected from exposure.

What is driving force for better containment processes, and what are the challenges facing manufacturers? An increase in the number of highly active substances, and much more restrictive regulations in terms of operations and environmental safety, has brought a signiﬁcant growth in the demand for containment installations across the globe.

Highly potent active ingredients such as hormones, retinoids, certain antibiotics and some narcotic substances require special containment during processing. This is deﬁned by the occupational exposure limit (OEL) or occupational exposure band (OEB) assigned for the active drug substance.

Current technologies available to minimise high potency risk Historically, personal protection equipment has been used for risk protection. However, whilst being undeniably important in providing protection to employees, there is a present risk of cross contamination in the working area through product transfer from containment suits, as well as uncomfortable working conditions. In order to protect equipment operators and decrease the levels of product contamination from microgram to nanogram levels, it has been necessary for the pharmaceutical industry to advance its containment strategies.

Increasingly potent drugs have required the industry to implement dramatic changes in plant design and operating procedures to ensure adequate containment. However, current expectations of levels of containment often far exceed the capabilities of equipment designed and manufactured only a few years ago. When selecting sealing components for high containment applications, it is essential to consider the potential problems which may arise in the event of a leak or valve seal failure: • Operator exposure: Employees and the general public must be protected from the product. Exposure to just a small quantity of a highly potent compound can pose signiﬁcant health risks. • Cross-contamination: There is a particular risk for patient safety in relation to the quality of the product in production. In order to satisfy the requirements on contamination protection in production, efﬁcient technologies are vital.

where space and existing equipment constraints limit the options available. These valves have demonstrated the ability to meet the containment targets required for handling APIs. SBVs minimise the amount of airborne particle exposure during the transfer of potent powders from one process step to the next. A fundamental feature of all SBVs is that they consist of two halves which dock together, namely the active ‘Alpha’ unit and the passive ‘Beta’ unit. Each half consists of half of the ‘butterﬂy’ disc, which is sealed against the main body with an elastomeric seal to create a high containment facility. Elastomer seals are used within each half as a ‘seat’, providing an effective containment seal between the active and passive halves once docked together.

Sealing challenges in containment processes Valves and the elastomer components within them are routinely exposed to a variety of chemicals and solvents, such as aggressive cleaning agents. Therefore, the chemical compatibility of the elastomer material within any containment process is a critically important design consideration. Valve manufacturers have long relied on materials such as EPDM (ethylene propylene terpolymer) as a material of choice for pharmaceutical SBV seats. However, with API potency on the rise, there is a requirement for more resilient elastomer materials.

• Split butterﬂy valves (SBVs)

PPE recommends the use of perﬂuoroelastomer (FFKM) seats, in such chemically aggressive applications. The outstanding mechanical properties of FFKM, combined with almost universal chemical resistance (similar to that of PTFE) and excellent thermal capabilities (from -30 °C to +325 °C), make it ideal for SBVs used in high-potency API processing environments.

However, challenges can arise when trying to ﬁnd containment solutions for existing equipment and facilities. It is with this consideration that PPE believes the addition of a SBV can prove to be a cost-effective solution, particularly

Through simple equipment and material considerations, such as using FFKM seats instead of EPDM ones in SBVs, it may be possible to extend the operational capabilities of a high containment valve without expensive redesigns.

There are three containment approaches which are typically utilised: • Downﬂow booths and extracted tables • Isolators and gloveboxes

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Protect your operator and your product

DPTE® Single Use Sterile Transfer Solutions The DPTE® system is installed in most pharmaceutical production lines for product and operator protection. DPTE® Alpha and Beta: a true match for perfect fit, jointly validated for highly secure transfer.

For more information: www.getinge.com/lifescience

COVER STORY

Lightening the load Handling materials in pharmaceutical manufacturing is challenging, time-consuming and costly. Many manufacturers repeatedly struggle with the same issues — even designing whole facilities to work around handling problems. The team behind PuroVaso saw an opportunity to design an entirely new solution for moving and storing that was better suited to modern manufacturing processes. Here, they tell us more…

oving and storing powders, granules, tablets and capsules can be a challenge. Available containers range from cumbersome to fiddly. Fibre drums are difficult to keep clean. Stainless-steel containers are heavy. IBCs are huge. Looking at a Cardboard boxes are easily damaged. Plastic bags and broad range liners are flimsy. of criteria is

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integral in the design of a container solution that meets the needs of modern pharmaceutical manufacturing.

These solutions are often expensive requiring capital investment, or singleuse and environmentally unsustainable. Most are difﬁcult to handle requiring more capital equipment. The problem is never more evident than when operators are forced to use a lifting hoist or a stacker truck to handle very small volumes of active ingredients that could easily be handled manually.

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Working around these challenges takes a great deal of care and adds a lot of time to each manufacturing process.

A broad range of criteria As reported by Health and Safety Executive (HSE) manual handling within pharma accounts for two thirds of instances involving the reporting of injuries, diseases and dangerous occurrences regulations (RIDDOR’s).1 To make this aspect of a working environment safer however, is not simply a case of reducing the weight that is to be handled manually there are many other important contributory factors. Looking at a broad range of criteria is integral in the design of a container solution that meets the needs of modern pharmaceutical manufacturing. From the container material to its overall ease of use — below we break down the major considerations, highlighting their importance to design and handler safety.

Material Making a container for any form of handling requires a certain level of fore-thought, will the contents be heavy/light, hot/cold, will they react to certain compounds/materials, etc. This factor is of great import to pharmaceutical ingredients, which are governed themselves by strict regulatory guidelines and therefore should be kept at optimum condition while in storage or in transit. Suitable materials for use in such containers include those that are manufactured from US, EU and UK regulatory compliant starting materials and that meet various regulatory bodies’ requirements. One such example is anti-static polyethylene, which is used in standard PuroVaso containers. This is recognised as one of the most chemically suitable materials for pharmaceutical manufacturing and is also suitable for ATEX dust environments. To help visualise the ﬁll level of the container it is possible to use a translucent opaque white formulation and in cases where UV protection is required a pure white formulation can be used. Conductive polyethylene can also be employed, allowing electrostatic charges generated by the powders or granules to be dissipated. This material is particularly relevant for micronized APIs, electrostatic static sensitive excipients or for higher risk ATEX dust and gas/vapour environments. Using a material like polyethylene in a container affords multiple advantages. Not only is it lightweight compared to other materials but it is also structurally stable. These beneﬁts mean that handling of the container is made easier while also ensuring protection of the product contained as it can sustain being dropped without the risk of leaking or spilling.

Task Thinking about the duration of time a container will need to be handled as well as how often is important in container design. As mentioned above, use of a lightweight yet sturdy material is greatly beneﬁcial but the size of the container and the ergonomics should also be thought about.

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Containers should be small enough that they are easy to carry whether full or empty. Having a square shape means they should ﬁt into usually limited storage space in containment facilities but using rounded edges also minimises any potential risk of slipping when loading.

Ease of use and environmental factors Ensuring ﬂexibility for the users’ requirements is also important. The neck of the PuroVaso container, for example, includes an industry standard tri-clamp ferrule, which allows any valve to be ﬁtted. Additionally, a full range of ancillary devices means the containers can be interfaced with all existing pharma equipment. Whether single-use or multi-use, products nowadays should be designed to meet requirements while avoiding adverse impact on the environment. If designing a single-use product then using a fully recyclable material is advantageous. For multiple use products then ability to clean appropriately is an important consideration. Having a large internal radius and rounded corners helps facilitate cleaning and the material used should be able to withstand cleaning at high temperatures with detergents and sterilising agents. Further to these requirements, PuroVaso has been designed so that sterilisation with VHP or gamma irradiation can be performed.

Summary It isn’t easy to develop an entirely new consumable product for use within the pharma sector. Many factors need to be considered in the design process. Ensuring that not only cost is viewed but also the practicality and safety for the day-to-day use is deﬁnitely imperative.

Reference: 1. http://www.hse.gov.uk/pharmaceuticals/issues/manualhandling.htm

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DEVELOP & MANUFACTURE

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BIOLOGICS MANUFACTURING Boxed off: The KUBio modular manufacturing solution offers pre-fabricated modules that can be delivered in a shorter time-frame compared with traditional pharmaceutical factory builds

What’s in the box? How the flatpack concept is a winner with biologics manufacturers As the manufacture of biologics takes on increased significance in the pharmaceutical sector, it’s clear to see why GE Healthcare’s KUBio system is growing in popularity. Lu Rahman paid a visit to the company facility in Uppsala, Sweden to find out why this approach is indeed, so ground-breaking

f the concept of a biopharmaceutical manufacturing facility arriving in a box seems far-fetched, think again. It’s becoming the norm for GE Healthcare customers. Combining manufacturing excellence with healthcare expertise, the company’s KUBio modular manufacturing solution based on single-use technologies – which is being hailed as a ‘game-changer’ for the biopharmaceutical sector – offers pre-fabricated modules that can be delivered in a shorter time-frame compared with traditional pharmaceutical factory builds. This of course creates costefficiency benefits for manufacturers. It was interesting to learn more about this concept – which has piqued much interest within the biopharmaceutical sector – at GE Healthcare’s Uppsala facility. The manufacture of biologics has grown in recent years: According to Grand View Research, the global biologics market is anticipated to reach $399.5 billion by 2025. Drug manufacturers in this space are therefore looking for cost-effective and efficient ways of bringing their products to market. Investment in a biopharma facility for the development of a new drug usually takes three to four years. At this point the drug is usually only in phase 1 development, highlighting the financial risk of the process can pose. KUBio construction typically takes half the amount of time to be planned, constructed and installed. KUBio has been designed to provide an innovative offthe-shelf, modular factory that will save manufacturers of biopharmaceuticals time and money. The pre-made modules – equipped with GE Healthcare’s technologies – are assembled at a customer’s chosen site to make a fully

functional ready-to-run bioprocessing facility. This says GE Healthcare is faster to install than having to construct a traditional factory.

also allowing them to dramatically decrease/reduce a typical construction time and greatly streamline the whole construction process,” added Donati

So how does the system work? Customers are assigned a dedicated project manager from start to finish offering continuous communication between GE Healthcare and the client, and to ensure that the user receives a product to its exact specification. With strong post-delivery support to aid successful installation, training and qualification, the process is designed to offer a premium product that meets the precise needs of the client. KUBio is designed to meet cGMP requirements while optimising manufacturing flexibility and productivity.

The introduction of KUBio expands GE Healthcare’s offering of world-class tools, technologies and services for the biopharmaceutical manufacturing industry, allowing customers to benefit from a range of solutions that can be tailored to meet specific needs, from pilot to commercial scale. GE Healthcare’s KUBio comprises start-to-finish services and single-use technologies, such as Xcellerex and WAVE bioreactors, mixers, filtration and chromatography systems, which are all integrated through a single automation platform.

Daria Donati, director, business development and innovation enterprise solutions at GE Healthcare Life Sciences, said: “Collaboration is a crucial part of the project and is maintained from start to finish. GE Healthcare expertise is utilised on both the application of the technology and the way we engineer the system. Throughout the process standards are maintained to the highest level to ensure we fulfil the requirements of industrial manufacturing.” From the initial quote to ten years after-delivery support, GE Healthcare maintains close contact with the customer. The modules are produced in a controlled environment to ensure quality from the start. They include the specific materials required by the customer for that room – electricity, water and ventilation. “KUBio is a new way of manufacturing biopharmaceuticals, bringing our customers a simplified way to build a facility

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Expanding services: KUBio expands GE Healthcare’s technologies and services for the biopharmaceutical manufacturing industry

PROCESS EQUIPMENT

Necessary evil or process champion? The truth about vacuum conveying… Commonly overlooked or the first item to be axed when budgets get cut, vacuum conveying is often considered a necessary evil in processing and installed retrospectively. Yet, as Andrew Turner from Hanningfield Process Systems reveals if it is well-designed it can be a process champion…

acuum conveying or pneumatic transfer is often regarded as a necessary evil in processing. Why spend money on a system which does not alter the process or add value?! Commonly overlooked at the design stage, or the ﬁrst item to be axed when budgets get tight, vacuum conveying is typically installed Vacuum conveying or retrospectively, perhaps prompted by an pneumatic transfer is often operator injury or containment breach. regarded as a necessary evil It is often shoe-horned into tight spaces (both height and footprint), with signal in processing. Why spend lines and hoses following tortuous routes money on a system which around existing equipment — and giving does not alter the process these versatile and much maligned systems or add value? a bad reputation.

The raw material is first loaded into a high-shear mixer/granulator. This may include active, excipients and a binder, all of which need to be introduced into the mixer bowl, which is generally raised off the suite floor on a podium, and accessed by steps. Once mixed and granulated, the wet granulate is passed through a mill to remove oversize lumps, and into a fluid bed dryer where it is dried in a bed of moisture-controlled air. The dried granule is then passed through a second mill to remove agglomerates formed in the drying process, and then into bins or IBCs for onward movement to tabletting etc.

The truth about vacuum conveying is quite the opposite, and a well-designed system can enhance a process, increasing throughput and efﬁciency, eliminating the risk of operator injury and exposure, and ensuring product containment — whilst being kept tidy and compact.

The process of loading the dry ingredients for a large production batch into a mixer/granulator by hand involves an operator manhandling drums of weighed product up podium steps, and tipping it into the opened lid. This not only exposes the operator to the product (often requiring gloves and mask to prevent contact, inhalation, exposure to eyes etc.), but can often lead to injuries on the steps, manual handling issues, minor batch losses, and airborne dust. It can also be a slow process, and is prone to errors in matching the recipe.

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The problem The typical integrated pharmaceutical granulation suite is perhaps the best example of these principles being optimally applied. These suites vary across the industry, dependant on factors such as batch size, the nature of the product, binder type and so on, but will typically comprise a number of distinct processes turning raw material into granule, for onward processing — perhaps into tablet or capsule form.

The movement of the wet mass from high-shear mixer, through the wet mill, and into the dryer bowl is most commonly achieved under gravity (the reason for raising the mixer on a podium), but it is the initial loading and ﬁnal unloading where vacuum transfer is relevant.

Once dried, the dryer bowl can be removed, breaking the containment seal, and the granule manually removed by scoop. It is tipped into the dry mill, then feeding into the bin below under gravity — all very labour intensive and time consuming. Due to the ergonomics of this process for the operator, the dispensing height of the dry mill dictates the use of a relatively small destination bin beneath it — and this then often needs to be transferred into a larger vessel/IBC for onward movement, introducing yet another step, and increasing batch losses and operator exposure during this additional transfer.

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The solution

Conclusion

The solution at both stages is simple — transfer the product under vacuum. The operator can tip the bag/drum of product directly into a sack-tip station at ﬂoor level, or can plunge a vacuum lance (akin to a domestic vacuum cleaner nozzle) into the bag or drum, eliminating the need to climb the podium steps. For more hazardous products, there are other means of unloading the supply containers without breaking the seal. The vacuum transfer system pulls the raw materials from this station or lance up to a hopper over the high-shear granulator, and drops it into the bowl in a contained manner. The sack-tip station may be supplied with a hood and/or curtain with dust extraction, to ensure there is no airborne dust in the room and negates the risk of operator exposure. Loading is fast and efﬁcient from the point of unloading the supply drum/sack, and a large batch can be loaded into the granulator in a matter of minutes, for the wet granulation process to commence.

As with any piece of equipment, there will be exceptions, vacuum transfer will not lend itself to all applications, but in the majority of cases it will be of huge benefit to the process. If lateral movement is required between operations for dry material, then vacuum conveying should always be a serious consideration. Dry product (powder, granule, flake, chips, even tablets) can be transferred safely under vacuum, without the risk of injury, in a contained manner, eliminating airborne dust and operator exposure. Add to this the fact that the inclusion of a pneumatic conveying system can speed up product transfer considerably, increasing efficiency and reducing batch process times — and you would have to ask why would you not include such a beneficial piece of equipment?

Once dried, instead of separating the bowl from the dryer body and exposing the product, a vacuum conveying system is connected to the discharge valve just above the plate. The bed is fluidised and the vacuum turned on. Dried product is raised as a fluid bed, and flows out of the discharge port, drawn by the vacuum. Again, the unloading of large batches can be achieved in minutes, far quicker than by manual unloading. The vacuum system may also be sized to incorporate a dry mill (to remove agglomerates formed in the drying process) as part of the transfer. This vacuum swept milling is again faster than milling under gravity and is done so in a totally contained manner. The milled product is drawn into a transfer hopper and deposited into the destination vessel (drum, IBC etc.). The operator has had no involvement in this process other than making and breaking the transfer hose connections before and after, and operating the vacuum conveying system.

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PROCESS EQUIPMENT

Pull out all the stops In this article, Stephen Morley from Steelco, looks at the new developments in stopper processing equipment.

or more than two decades, stopper processors (or more generically, closure processors) have fallen into two categories: rotating drum style machines and systems in which the processing vessel is detachable and mobile for transfer of the treated components to the downstream process. While both target the same result for the closures — cleaning, (siliconisation), sterilisation and drying — each has their own merits in terms of the workflow/production application: the rotating drum style was primarily adopted for high capacity production; while the mobile processing vessel solution was and remains mainly suited to feeding a high throughput barrier isolated filling line. In more recent years, there has been an increasing focus on single use technologies, with a trend towards the use of ported bags for delivery of clean and pre-sterilised ‘ready to use’ closures to isolated filling lines. Such solutions are ideal for smaller scale, lower speed lines under barrier isolation, but have practical and financial challenges as line speed increases. As the market for such systems has developed, so too has the need for systems for processing the closures and filling them into the ported bags — automated bag filling with accurate dosing capability. While the capacity/output requirement of the stopper processor for this application may be similar to that of a high speed/high throughput filling line, this application is quite a different challenge. Whatever the workflow, usage pattern or equipment style, all current commercially available stopper processors operate as a batch process, with, until now, several steps of manual handling, often requiring the installation and operation of heavy duty mechanical lifting equipment in the GMP manufacturing area. Irrespective of manufacturer, for point-of-use processing (i.e., not stopper manufacturing), both loading and unloading of closures is traditionally performed manually, in GMP controlled space. Loading typically requires manual opening of bags followed by manual transfer into the processor, for example using a hopper or funnel. Unloading of treated closures from the processor typically involves use of a mechanical device to lift, rotate and position the processing or transfer vessel close to the infeed hopper of the filling line and then transfer the closures via some form of transfer port (typically but not always a rapid transfer port).

Most usually, the processing or transfer vessel is an insulated stainless steel pressure vessel and typically weighs more than one hundred kilograms when full. As such the lifting equipment must typically be integrated with the building structure and requires significant height in the cleanroom to be able to place the outlet of the vessel above the hopper to enable gravity transfer. Additionally, while suitable for elastomeric/rubber components, this gravity feed system can be problematic for more delicate closures such as crimp caps and lined seals. Stopper processors represent a significant capital investment and typically have a lifetime of more than 20 years. The market is rapidly evolving, and moving towards flexibility of design, with filling lines capable of handling multiple formats, and incorporating continuously developing single use technologies. With this in mind, the stopper processor must also be flexible and adaptable to be able to maximise the return on the investment over the lifetime of the equipment. With these trends and challenges in mind, Steelco (Riese Pio, Italy) redesigned the ICOS brand stopper processor and introduced the SPE, or stopper processing equipment. Based on the LST model, the SPE is available in a range of capacities, to suit a variety of filling line speeds, as well as the production needs of stopper manufacturers. Moreover, the processor may be automatically loaded, incorporating a visual inspection system for an automated line clearance check to avoid cross-contamination between batches. The loading infeed may be outside the fill-finish suite/clean area such that cartons, bags and the initial manual operations are in a lower grade area. The SPE processing chamber is designed to allow multiple discharge/offload systems to be configured, with simple retasking of the processor for: • Ported bagging systems - DPTE or Sartorius Biosafe • Heat sealed bags • Ported pre-sterilised containers (pre-sterilised as part of the treatment process)

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As example, a full load/treated batch of closures may be sub-divided into one or more DPTE ported transfer vessels for delivery to a barrier isolated filling line. Multiple, smaller transfer containers allow less heavy duty lifting equipment to be used, and require less height in the clean area. This latter option combines the benefits of the rotating drum style processor with that of the mobile transfer vessel solution. As the ultimate solution for high throughput applications, direct connection of the output port to the filling line is also possible, allowing seamless, fully automated processing and delivery with no manual intervention. With the advent of the routine use of barrier isolators in the pharmaceutical industry during the early 1990’s, stopper processing equipment underwent a step-change to adapt to the challenges presented by isolation technology. In recent years, the adoption of single use technologies has gone some way to fill the gap where the capital expense of local stopper processing for smaller scale production cannot be justified. However, it is clear that challenges and gaps in the stopper processing equipment portfolio remains, and there is a need for continued innovation in flexible, configurable and retaskable solutions.

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COLD CHAIN SOLUTIONS

Cold comfort… is automation a revolution in vaccine delivery? We speak with the CEO of Controlant, Gisli Herjolfsson, about the company and its cold chain solutions that are revolutionising delivery of vaccines to developing countries and more.

Q. Could you give us a brief overview of Controlant? A. Controlant was founded in 2007 and grew out of a collaborative project by our founders aiming to develop wireless sensor technology that could feed into a centralised database while we were students at the University of Iceland. It was the arrival of H1N1 in 2009, better known as Swine Flu, however which concentrated our efforts. Iceland’s Directorate of Health acquired large quantities of the H1N1 vaccine as a proactive means to protect the country’s population but they were concerned that the storage coolers located throughout the country weren't reliable enough for the vaccine. A quick solution was needed. We set out to develop our technology and services to protect the vaccines while en route to their intended destinations. Now the entire end-to-end pharma cold chain in Iceland has become monitored on a single platform reducing the total waste to below 0.3%. This inspired us to our current mission that is to reduce global waste due to temperature excursions in the pharmaceutical cold chains to 0.5%. Our company has become a global leader in transforming and protecting cold-chains in the pharmaceutical, food and cold chain logistics sectors in more than 100 countries worldwide. Our subscription approach, coldchain-as a-service (CHaaS), combines a web-enabled, cloud-based software platform with prescriptive analytics, powered by wireless, realtime IoT loggers with condition-monitoring, location aware sensors, and a powerful layer of automated logistics services.

Q. Why are cold chain solutions necessary? A. First and foremost, it’s about patient safety. Each medicine and vaccine transported through the supply chain is ultimately used by a human being. Cold chain monitoring solutions are needed to ensure that medical products maintain their integrity from the time they leave a manufacturing facility until they’re delivered to a hospital, clinic, or pharmacy, which means that continuous temperature and condition monitoring is a necessary part of the process. Generally, innovative cold chain monitoring solutions are needed to help reduce the staggering losses in global supply chains and

to satisfy applicable regulations. Pharmaceutical losses add up to an estimated $5.4 billion globally and are expected to increase as patient demand continues to grow. Temperature variations in excursions are responsible for the degradation of up to 35% of the world’s vaccines. The problem has been compounded by the nature of data collection for perishables: many siloed points along the supply chain lack network connectivity, and data collected by conditionmonitoring devices — while current when it is collected — is not always immediately available for review and analysis to assess and ensure relative remaining shelf life, quality, or efﬁcacy of products at the end of the supply chain.

Q. What challenges do companies face when trying to deliver vaccines/products to various countries? A. The cold chain is constantly changing, which makes it difﬁcult to anticipate and mitigate against all risks. There are logistical issues involved with shipping products that travel for long distances or through multiple countries, each carrying its own unique set of challenges. For instance, there may be an inadequate number of designated truck stops along a shipment route in a particular country. Truck drivers may need to pull over into an unmonitored parking lot to rest, which places a shipment at risk of theft. The regulatory landscape poses a different set of challenges. It may take less time to ship a product by air into a particular country, but due to its regulations and backlog, those products may sit in customs for weeks or months, placing temperature-sensitive products at risk, and therefore, it may be more efﬁcient to send shipments via sea freight instead. Supply chain complexity means that there are a number of stakeholders involved, including those from operations and quality, as well as logistics partners. They may all need shipment information, but historically, would only receive ad hoc data at the end of a shipment — which has limited stakeholders to documenting only what happened, and only after it happened.

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Q. Are there specific issues surrounding developing countries and how does your solution help overcome these? A. Many developing countries lack the infrastructure needed to efficiently and safely deliver vaccines — and yet, immunisation is one of the most important health interventions for children. There may be a lack of electricity to store supplies, and roads and other conditions make it difficult to reach certain areas, which means there is potentially a greater requirement for innovative products. Political conflict, migration and corruption are further barriers to vaccine access in these areas. There are challenges to connecting stakeholders in developing areas together with shared access to the supply chain: government organisations and agencies, NGO’s and private groups may all be involved with vaccine delivery, but there has been a lack of visibility over product and supply data that could help with distribution and intervention efforts. Individuals may travel for days to reach a medical clinic, only to find that there isn’t any vaccine supply available. There is significant potential for new technology to help solve these challenges while having a significant impact.

Q. What differentiates your solution from other available options? A. Customers only pay as they go for what they use, rather than purchase loggers up front; we call it cold chain as a service, or CHaaS: our trifecta of solutions — cloud software with prescriptive analytics, IoT loggers, and automated logistics services — are subscriptionbased, offering a cost-effective solution for businesses, which can scale up their operations as their needs evolve. With CHaaS, less upfront investment in human resources, processes and equipment is needed, while companies can gain access to the expertise needed that is directly relevant experience solving speciﬁc problems spanning across the supply chain.

For instance, with that data, we can trace shipments, routes and collect data along the way that places shipments at a higher risk given seasonality or weather patterns, and suggest the best routes to take, given those factors. This means that businesses can increase their operational efﬁciency, mitigate the risk of damage and waste, and increase their overall proﬁtability.

Q. Will this solution enable users to remain fully compliant? A. Our solutions are designed and manufactured with compliance as a key factor in mind. Good distribution practices (GDP), good manufacturing practices (GMP) and 21 CFR Part 11 compliance are primary concerns of our customers. Quality management and control are critical to our own business; we follow GDP and GMP, and are ISO 9001:2015 Quality Management system certiﬁed.

Q. Are there any limitations to the automated solution? A. Adopting a cloud solution with real-time data requires stakeholder buy-in and internal processes to fully leverage the advantages that shipment and supply chain visibility offers. Our solutions are built for global shipments, via road, air and sea, for both primary and secondary distribution, so there may be many different stakeholders involved. Our team operates as a virtual partner to our clients, facilitating the adoption and implementation of our solution, often providing services and expertise needed to supplement existing resources and constraints. Part of our work is in helping businesses to successfully navigate through their digital transformation, embrace change and build sustainable, cost-effective cold chains that will lead them into the future.

Q. Where do you see cold chain services in 10 years’ time? Q. In your opinion, what advantages does an automated system offer clients and patients? A. In our minds, automation and data aren’t the future — they’re table stakes. Data automation is necessary for businesses looking to streamline and effectively scale their logistics in a sustainable manner. Descriptive analytics enable stakeholders with the ability to control their cold chains and make better business decisions. Data automation provides additional opportunities to generate prescriptive analytics for informed forecasting — not only telling businesses what will be the likely outcome based on historical data, but also why.

A. In 10 years, we think we’ll see a shift to products being delivered directly to patients, which will mean that distributors and delivery service providers will need to ensure that temperature-sensitive assets maintain integrity through the last steps of their journey and remain safe for consumption. We think that businesses of the future will adopt real-time visibility solutions and look to managed service providers in order to gain the cost structure, technology and collaboration opportunities with stakeholders across networks, to automate logistics, scale faster than their competition, better serve customers and partners and proactively protect their brand.

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s ’ w o r r o m To d l r o w

LOGISTICS

Scott Allison, president, Life Sciences & Healthcare Sector, DHL, gives us a rundown of the connected warehouse and how innovations in logistics are benefitting this rapidly changing world.

efore you can optimise a function, you must ﬁrst be able to visualise it. Running a life sciences and healthcare warehouse provides a great example of this.

Key operations in the warehouse include receiving, sorting, storing and shipping pharmaceuticals in precise and correct quantities. These goods must be safely protected from temperature excursions, shock and water ingress. Warehouse personnel must strive to meticulously record and label each item of stock, as well as strategically position and schedule everything for timely rotation. Batches of pharmaceuticals must be ready for shipment as soon as the next dispatch request comes in. So how can today’s pharmaceutical manufacturer visualise these functions? It takes logistics innovation and the application of technology. By fully digitising the warehouse, all physical entities can be deﬁned in bits and bytes — from objects such as blister packs of prescription meds and the crates they are packed in to the equipment that is being used, such as conveyors, forklifts and numbered racks and shelves, and even to the people who are working in the warehouse. Once all physical entities in the warehouse have been described by unique data blocks, they correspond to virtual objects which can be usefully manipulated. This data can be crunched and analysed in exquisite depth. It can be subjected to sophisticated ‘what-if’ scenarios. It can be combined for greater customer centricity and much more.

Augmenting reality With another customer — one of the world’s premier biopharmaceutical companies — we are piloting an innovative warehouse ‘vision picking’ solution in Australia. Together we hope to establish whether augmented reality smart glasses can be used for order picking in a more cost-efﬁcient manner than standard manual scanning processes. Warehouse personnel see the digital picking list and the optimal warehouse route in their ﬁeld of vision (an ‘augmented’ view) to save time, reduce errors and enable real-time inventory updates. Similar pilots with other companies in Mexico and in the Netherlands have achieved 15–25% productivity gains.

IoT tagging Many of our pharmaceutical customers are using Internet of Things (IoT)-enabled tagging technology to gain tighter control of product inventories and reducing waste while increasing service levels and availability. This stronger link between physical products and data also empowers each organisation in its efforts to eliminate theft and counterfeiting.

Smart sensing Many of our customers have embarked on a digitalisation journey that embraces the concept of the connected warehouse, seeking to create new efﬁciencies and secure higher levels of productivity while lowering operational costs and gaining competitive edge. Let me share just a few examples.

Deploying robots

In addition, most of our pharmaceutical customers are using smart sensor RFID technology to track the temperature of inventory across their warehouses and distribution centres. This not only protects the integrity of highly temperature-sensitive and valuable products, but also ensures compliance with stringent quality regulations. In our own global network, we have more than 100 certiﬁed life sciences stations providing monitoring, intervention and storage services according to industry-speciﬁc GDP standards.

One customer — a multinational chemical, pharmaceutical and life sciences company — recognised that time was being wasted during product packing because warehouse personnel had to walk long distances inside a vast warehouse. By equipping the facility with wiﬁ infrastructure beacons, robots can now be deployed to undertake this timeconsuming task. These machines can precisely locate digitally tagged items anywhere in the warehouse and travel safely thanks to heat maps that clearly track the movement of assets and people throughout the warehouse. Meanwhile, with more time on their hands, the human packers can take on more specialist and value-adding tasks in the warehouse.

In the connected warehouse, logistics innovation and technology are enabling pharmaceutical companies to tackle many different challenges in a changing world. So, it comes as no surprise that logistics managers are very keen to explore digital transformation and see the latest trends and innovations at ﬁrst hand. It was my recent pleasure and privilege to accompany delegates at DHL Global Life Sciences and Healthcare Conference in Singapore on a tour of DHL’s Advanced Regional Center. This new multi-user hub includes a large-scale multi-shuttle solution capable of handling product throughout the facility 24/7. To witness this makes you feel that anything is possible in the connected life sciences and healthcare warehouse of tomorrow!

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COVER STORY

Join the complete North American pharma supply chain under one roof!

April 24-26, 2018

Pennsylvania Convention Center Philadelphia, PA, USA cphinorthamerica.com

Join the epicenter for pharma innovation, emerging trends, insights, and education in North America! CPhI North America is your opportunity to meet the entire pharma eco-system, from early discovery to commercialization, offering you access to the right partners at any stage of development. With over 7,400 attendees and 630+ exhibitors together for three days, this is your chance to network with top industry players, learn about the latest trends and regulations, and effectively do business. Use Promo Code RLS18 when you register to claim your FREE Expo Only pass or get an additional $50 off your Conference or VIP Pass. Go to cphinorthamerica.com/register today!

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TECH TALK

A new era for pharma Here, Dr Neil Polwart, Novarum founder and BBI group head of mobile, goes into greater detail about how digital technologies will herald a new era for pharma.

ate last year the FDA cleared a pill with an inbuilt ingestion tracking system. Remarkably, the tablets have an inbuilt sensor that is aware when the medication has been taken and data is transmitted to a patch worn outside the body. This lets clinicians know whether patients have been taking the prescribed dose of medication needed to treat their mental health condition. Only a few years ago, such technology would have seemed like science ﬁction and the idea that the FDA would have embraced it would have seemed just as farfetched. Does this herald a new era for pharmaceuticals where every drug will need to be augmented with an ingestible pill and proprietary monitoring system? Probably not. There will, however, be digital technologies that can complement a far wider range of treatments.

While patient compliance is a challenge across the pharmaceutical industry, some areas of healthcare are more vulnerable than others. Management of conditions like cholesterol present circumstances where patients don’t see The digital revolution or feel rapid symptomatic beneﬁt. In means that most patients these cases, compliance can be more problematic than for patients who can already have technology directly link the medication to a physical in their pocket loaded improvement in their condition and are with an array of sensors therefore motivated to continue treatment.

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and communication technology.

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Likewise, the timing, mode of administration and frequency have an impact on patient compliance — taking one tablet first thing in the morning is an easy routine to adhere to, compared to having an injection on every three days, for example. However, only the most complex situations would benefit from having ingestible pills (or similar tracking technologies for other drug formats). Most patients aren’t aiming to deceive, they simply forget or lose motivation to maintain their treatment regime. The digital revolution means that most patients already have technology in their pocket loaded with an array of sensors and communication technology. By comparison, the patient information leaflets that are supplied with drugs, lack user-friendliness and interactivity. Even the most routine over the counter medicines could build both brand loyalty and provide meaningful, accessible, useful patient information with the introduction of interactive mobile apps.

How many of us have taken paracetamol (acetaminophen) for a headache, for the symptoms to recur shortly after, only to be uncertain when we took the original dose? Imagine a QR code on the packaging which seamlessly helped you track your usage, perhaps also providing warnings about incompatible medications and alerting the user about the risk of prolonged usage patterns. What if your prescription dosage was automatically uploaded to your phone and prompted you with reminders? Perhaps you could confirm you had taken the dose or ‘snooze’ the alert till later? You could also log some simple symptomatic observations, all of which might be easily summarised to help prompt discussion with your doctor and optimise future treatment. Of course, we are already starting to see sophisticated usage trackers getting added to inhaler technology. Meanwhile, as insulin pumps become ever more sophisticated, they can provide a wealth of information back to clinicians and patients alike. They may become swamped with data and we will need intelligent decision support tools to help extract the pertinent data. This could provide an opportunity for pharmaceutical manufacturers to differentiate products in competitive spaces. However, none of these technologies provide any real-time information on the effectiveness of the dose — if what you really want to track is the concentration of the drug in serum, it may be better to do exactly that. Indeed, there is growing interest in the pharma world towards adding complementary diagnostics to their therapeutics, these would be able to track a condition specific biomarker, the drug itself, or in the case of biologic drugs — antibodies to the drug. Patient convenience means that if the therapy is being administered at home, it’s likely this monitoring would be performed by the patient themselves using simple point-of-care style diagnostics. Once again, the patient’s own phone becomes a useful tool to help provide instructions, record and share the result and even to measure the response on the test itself. In my mind, the question is no longer whether regulators will support clearance of such technology-supported-therapeutics, but rather which manufacturer is going to be at the forefront of the new era? As the tech giants like Apple, Google and Amazon increasingly join the mHealth (mobile health) space, the pharma giants will benefit from investing more in digital healthcare to ensure their value proposition remains strong and that they are not left behind.