THE CLOCK IS TICKING
BREAKING NEW GROUND
WHATEVER THE WEATHER
MISSING A TRICK? Highlighting four digital and brand trends as a useful reference for the pharmaceutical sector
the next medicine... We’ll develop it together.
As a leader for contract development and manufacturing, we at Lonza Pharma & Biotech are recognized for our reliable, high-quality services, global capacity, innovative technology platforms, and extensive experience. Our broad capabilities span across biologics, small molecules, bioconjugates, and cell and gene therapies. © 2018 Lonza. All rights reserved.
We manage projects from pre-clinical stage through commercialization, and our expertise covers both drug substance and drug product. We believe that the best outcome – for you and for your patients – can only come as a result of a successful collaboration. Together, we can solve the next challenge and bring your next medicine to life.
Visit pharma.lonza.com USA +1 201 316 9200 Japan +81 (0)3 6264 0600 Rest of world +41 61 316 81 11 Email email@example.com
Contents June 2018 | Volume 18 Issue 4 REGULARS 5 EDITOR’S DESK
Looking at the rise of the orphan drug market.
6 A SMALL DOSE
A brief round-up of some of the developments in the industry including a step in the right direction for oral insulin and an overview of Alantra Pharma’s Fast 50 index.
Discussing how to future-proof against the increasingly strict area of water management through outsourcing.
14 REGULATORY AFFAIRS
Assessing if you are ready for the falsified medicines directive and revealing what the right questions are when a revision to a guideline, specifically Annex 1, is made.
20 COVER STORY
Here, Vicki Young from Nalla highlights four digital trends being embraced by other sectors that could prove a useful starting point for pharma.
46 TECH TALK
Revealing development considerations for mHealth apps.
FEATURES 22 BIOLOGICS
Highlighting some examples of new technology in the ADC space and the challenges associated with manufacturing for gene therapies.
28 SOLID DOSAGE SOLUTIONS
Detailing some of the important considerations in solid dosage solutions and the advantages of dry granulation as an alternative to traditional wet granulation.
34 QUEEN’S AWARDS
Looking at some of this year’s winners of the Queen’s Awards for Enterprise in the Industrial Trade category.
37 PURIFICATION & FILTRATION
In this case study, Howorth Air Technology and Russell Finex reveal how combining expertise enabled them to create multiple customised solutions for a new production facility.
How to overcome the logistical challenges of shipping medicines all over the world and how to manage the cost of packaging while maintaining thermal performance.
44 LOGISTICS & DISTRIBUTION
We speak with Sergey Lazarev of AirBridgeCargo about what it means to be an IATA CEIV Pharma-certified company and what the future holds.
FE55 & FE75 WITH CONTAINMENT PACKAGE + Flat valve for a safe product feed + Hermetically-sealed and automatically-locking window flaps + Rapid Transfer Port (RTP) access points for removing or introducing components + Low-dust tablet discharge + Hepa-filter H13 + Human-Machine-Interface (HMI)
5 HEAD OFFICE
Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE.
A BOOMING MARKET… According to the latest orphan drug report from EvaluatePharma,1 worldwide orphan drug sales are expected to grow at double the rate of that anticipated for the non-orphan drug market.
Tel. +44 (0)1244 680222 Fax. +44 (0)1244 671074 Web: www.epmmagazine.com
editor felicity thomas firstname.lastname@example.org
So, what exactly is an orphan drug? Orphan drugs are those that have been specifically developed for the treatment or prevention of a ‘rare’ disease — one which is considered to be life-threatening or permanently disabling medical conditions affecting less than 5 in 10,000 people.
deputy group editor dave gray email@example.com head of content, life sciences lu rahman, firstname.lastname@example.org reporter reece armstrong email@example.com publisher duncan wood
PRODUCTION art robert wood
robert anderton tel: +44 (0)1244 952359, firstname.lastname@example.org shona newton tel: +44 (0)1244 952519, email@example.com head of media sales, plastics & life sciences lisa montgomery firstname.lastname@example.org
email@example.com qualifying readers Europe - Free, ROW - £249 outside qualifying criteria UK - FREE, ROW - £249 please subscribe online at www.epmmagazine.com Address changes should be emailed to firstname.lastname@example.org European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals. Volume 18 Issue 3 © May 2018 While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.
BPA Worldwide Membership ISSN No - 2052-4811
With worldwide orphan drug sales predicted to grow at a signiﬁcant rate and each drug fetching a hefty price tag, I look at this market and its drivers in a bit more detail…
Previously, pharma companies would focus more on the conditions that were affecting much larger patient populations. However, to tackle rare diseases affecting much smaller numbers of patients globally, incentives were introduced to motivate more companies to perform the lengthy and costly work of developing the required orphan drugs. Financial incentives set out in law — available in the US since 1983, Japan in 1993 and the EU in 1999 — to encourage pharma companies to put the time and
EDITOR’S DESK money into developing orphan drugs for these small patient populations, include options such as reduced research and development costs and funding. Additionally, companies that gain approval for marketing authorisation of an orphan drug also gain market exclusivity. In Europe, companies are granted 10 years of exclusivity from the time of approval, which is the same for the Japanese market.
In the US, this is a little less at seven years. This exclusivity means that regulatory bodies cannot approve the same product for the same orphan indication, leading to a significant control over what cost the companies can command for these drugs. In the latest EvaluatePharma analysis the mean cost per patient for orphan drugs came in at just under $150,000 per patient last year, which is four times that of the cost of non-orphan drugs. The most expensive drug (Soliris) actually weighed in at a cost of more than $500,000 per year. But, these prices could be coming into dispute, as the report also highlighted that, year-on-year, there is a reduction on the amount of price increases each orphan drug can command. This pushback could be the result of a rise in pressure from government and patient groups around drug pricing with some looking more closely at the incentives offered and questioning whether it is fair for big pharma to receive this aide. Yet, with demand continuing to be strong the market growth is still looking healthy overall. And with several drugs for rare diseases being touted as ‘ones to watch’ as predicted blockbusters for this year perhaps the question from the mid-noughties of ‘is this the end of the blockbuster?’ will transform into ‘which orphan drug will be the next top blockbuster?’ — only time will tell…
1 | http://www.evaluategroup.com/public/ Reports/EvaluatePharma-Orphan-DrugReport-2018.aspx
A small dose
N W O D THE ? H C T HA ORAL INSULIN COULD BE CLOSER THAN YOU THOUGHT... The ﬁrst oral form of insulin has taken a big step towards approval by the US Food and Drug Administration (FDA) recently. Why is this a big deal? Daily administration of insulin can be burdensome and difficult for many patients, with the injections taking time and for some being an unpleasant interruption of the day. However, other administration routes have been hampered due to the importance of getting
the therapy to the bloodstream intact. Oral delivery systems in particular have found themselves wanting in this arena as the digestive system can be too effective leaving the amount of insulin that can reach the bloodstream at insufficient levels.
launched its largest and most advanced clinical trial under the direction of the FDA, evaluating its oral insulin (an orally ingestible insulin capsule — ORMD-0801) in 240 patients with type 2 diabetes.
What is the breakthrough this time?
In an earlier trial, the company’s oral option for administration of insulin proved promising as a safe delivery method with no serious adverse events in a group of 180 patients over a course of 28 days.
New York based Oramed Pharmaceuticals has just
“This is our most important study to date,” said Oramed
CEO Nadav Kidron. “A year from now we will better know the potential of our drug to control and maintain blood glucose levels and will have further proof of the longer-term benefits of taking an oral pill versus an injection.” Data from this clinical trial is expected to be available early next year and is hoped to set the stage for final FDA studies needed prior to approval.
Brexit comment - impact on AMR Eye on drug delivery A new project from the Chemelot Institute for Science and Technology (InSciTe, The Netherlands) is set to enter clinical testing. The Ocular Coil Drug Delivery Comfort Trial (OCDC) project will assess an innovative eye implant — a small ﬂexible coil — that can be positioned under the eyelid and deliver a drug via a drug delivery matrix made of a unique biomaterial over a set period of time — weeks or months. “This method will give patients more freedom in treatment, accurate drug administration and there are no caregivers needed,” explained Professor Rudy Nuijts from the Maastricht University Medical Center+ (MUMC+), head of the OCDC-project. Common drug delivery systems are not always effective in the treatment of diseases like glaucoma and ocular inﬂammation and so an alternative method could improve treatment efficacy as well as patient adherence while also lowering unwanted side effects. The study will initially assess the comfort of the implant with placebo-filled coils in healthy subjects and there are plans to perform safety and efficacy tests with drug-loaded coils in the second half of this year.
The latest report from the Business, Energy and Industrial Strategy Committee has been released — which in fact is its ﬁnal one in a series of reports on speciﬁc sectors — highlighting a positive view on the approach so far by the government to the pharmaceutical sector in light of Brexit. However, what will the impact of Brexit potentially mean for the country’s continuing battle against antimicrobial resistance. Dr Peter Jackson, executive director of the AMR Centre, gives us his view on the report: “The fight against antimicrobial resistance (AMR) requires coordinated international effort. Leaving the European Union (EU) with no deal for the pharmaceutical sector could significantly impact this effort
and remove millions of pounds of potential funding from the UK AMR sector. “The AMR community in the UK is particularly concerned that vital EU AMR funding initiatives, such as the Innovative Medicines Initiative’s ENABLE and COMBACTE programs, will no longer accept UK applicants after Brexit. “Similarly, the European Investment Bank’s ‘Innovfin’ AMR debt instrument may no longer be available to support UK clinical trials. “We would urge the UK government to ensure that significant levels of R&D support remain available to UK companies to progress innovative treatments for drugresistant infections.
“Alongside this, there must be the right support to translate the scientific advances made in AMR at UK universities into the creation of new biotech companies so we can continue to do what the UK does best: develop new drugs to treat global healthcare problems. “The AMR Centre is leading the UK’s response to AMR and working on a number of projects with partner organisations in Europe. This work much must be able to progress unhindered postBrexit. “Whether the UK is in or out of the EU, the most important thing is that companies, in particular SMEs, can work together across borders to gain access to funding, expertise and capacity to develop their new antibiotics, vaccines and diagnostics.”
A small dose
The future’s bright…
New research from global investment banking and asset management ﬁrm, Alantra (which last year combined with Catalyst Corporate Finance) has revealed that the future is bright for UK pharmaceutical companies.
Businesses are grouped into four distinct sub-sectors — pharma outsourcing, pharmacy chains, development, wholesale and supply (DWS), and consulting. The companies ranking top in these include: ●
The Alantra Pharma Fast 50 Index — an annual ranking of non-listed UK pharmaceutical companies — has highlighted strong growth in the privately-owned sector with the top 10 businesses seeing sales growth on average by at least 43%. “The UK is rightly regarded as a world leader in the pharmaceutical and life sciences industry and beneath the well-known names of big pharma, it is home to a thriving community of privately-owned businesses that consistently deliver long-term value,” said Tom Cowap, a director in Alantra’s UK advisory business (formerly Catalyst Corporate Finance) who specialises in the Pharmaceutical sector. “Despite the fact that the industry is facing difficult challenges including the spectre of Brexit, tough pressure on margins, demanding regulatory scrutiny and issues such as the patent cliff, the companies in the Alantra Pharma Fast 50 have repeatedly managed to grow their sales at an impressive rate.”
According to the index, the fastest growing privately-owned pharma business in the UK is Qualasept Pharmaxo, which grew its sales by an average of 69% over the past two years. This makes it the second year running for the company to top the list.
Pharma outsourcing: SimbecOrion, a boutique contract research organisation with an average sales growth of 49% per year over the past two years. Pharmacy chains: Gorgemead, which trades as Cohens Chemist, where sales are up by 51% a year over the past two years. DWS: Immunocore, a biopharma business, with sales up by 61% a year over the past two years. Consulting: Random42, a specialist in medical animations, with sales up by 34% a year over the past two years.
A bitter pill to swallow? Comedian Roseanne Barr has perhaps been left with a bitter taste in the mouth after receiving a swift response to her tweet that partially blamed the sleeping pill, Ambien, for her social media discrepancies. Barr, who had been fired and her sitcom cancelled after making a series of racist tweets, had written that she had been ‘Ambien tweeting’ at two in the morning, implying the drug was partially to blame for her actions. In response, Sanofi US released a written statement and tweet stating: “While all pharmaceutical treatments have side effects, racism is not a known side effect of any Sanofi medication.” So, although some of Ambien’s listed side effects including the possibility of driving, walking or even having sex while sleeping when taking the sedative, Twitter outbursts of a racist nature are not listed among them…
MAKING HASTE IN THE DETECTION OF DESIGNER DRUGS Italian scientists have developed a method that allows them to accurately detect and identify designer drugs in record time. Designer drugs are those that are structurally or functionally similar to a controlled substance but differ sufficiently enough that they can avoid classification as illicit. As the numbers of such drugs are on the rise, they are not only causing law enforcement and regulatory agencies’ problems they are also posing a threat to public health. Current analytical detection methods that are used to test for drugs work by recognising and interacting with a specified drug molecule. However, with new designer
drugs the molecules are not yet known and so identification has be done from scratch, which is a lengthy process. To tackle the issues of identification and detection of these new psychoactive substances, researchers from the University of Padova (led by Fabrizio Mancin) have used nanoparticles with a coating that binds to most psychoactive substances. How does it work? Adding the coatednanoparticles to water containing psychoactive substances will see the formation of a new compound. It is this new compound — which is part nanoparticle, part drug — that can be analysed in a nuclear magnetic resonance (NMR) spectrometer.
It is possible to perform this analysis as the nanoparticle molecular structure is known and so can be eliminated from the resulting data from the NMR machine, which will enable the analysts to discern what other structures are present. This method will allow for ‘cocktails’ of drugs to be identified simultaneously and even with low concentrations of drugs due to the sensitivity afforded by NMR. “In principle,” Mancin wrote in his paper published in Chemical Science, “by using this protocol it should be possible to propose a tentative chemical structure of a new ‘designer’ drug a few hours after the seizure of a single tablet.”
So much more than a clean surface
Research & Development Technical Specialists Quality Built In Global Presence Complete Range Industry Experts Validation Innovation Experienced Collaborative It’s not just about the products. It’s more than just a clean surface. Contec prides itself on its longstanding technical expertise, innovation and commitment to quality. Continued improvements in lean manufacturing, safety initiatives, vertical global integration as well as Research and Development, drive our critical environments product range forward.
To get to know Contec’s hidden depths, give us call on +33 (0) 2 97 4376 98 or drop us a line at email@example.com
Opinion Outsourcing also brings with it the benefit of specialist human resources and knowledge on best practices.
DON’T MISS THE BOAT… ...on water management in pharmaceutical manufacturing. Here, Declan Maguire, operations director, Celtic Anglian Water & Alpheus Environmental, discusses how to future-proof in this increasingly strict area through outsourcing.
ike a fast-moving tide, the management of water is quietly but quickly emerging as a significant risk for the pharmaceutical manufacturing industry in Europe. Companies may be unaware of the ever-increasing water management obligations under the EU Industrial Emissions Directive, which industry experts believe will be maintained in UK law after Brexit. The old methods of water management employed by many companies, particularly in regards to wastewater management, simply won’t meet the tougher requirements of these new environmental standards and companies will face fines and potential disciplinary action. In order to be both compliant with emerging regulatory requirements and cost-efficient in the face of increasing pressures on global water resources in coming decades, companies will need to look at how they ‘future-proof’ their water management. With water technology developing at a rapid pace, the process of managing water in-house will also become progressively inefficient and financially unsustainable. This may lead companies to look to outsource this function.
12 OUTSOURCING — THERE’S NO TIME TO WASTE! Outsourcing has been a revolutionary force, leading to exponential growth and efficiencies across all industries. Yet for many companies, water management has stubbornly remained in-house. But there’s no time to waste. The environmental responsibilities of industry in Europe are set to increase in 2018, with EU regulators currently drafting a series of best practices that will heighten already-stringent obligations in the decade ahead. These new guidance documents will inevitably result in companies needing to raise the bar in the design, construction and operation of their facilities, specifically including water treatment. Industry experts agree that Brexit will likely not affect the relevant legislation in the UK, which it implemented along with other EU member states after the current EU Industrial Emissions Directive came into effect in 2013. Increasingly stringent laws in Europe (and beyond) are being implemented to manage the ever-growing pressures on the world’s water systems. Increasing demand intensity within relatively small areas of the globe will result in the over-harvesting of clean water for the purposes of providing drinking water for domestic use in future years. Meanwhile, industrial and commercial water customers are rightfully demanding better-quality water in order to produce better-quality products. Increasing levels of urbanisation and industrialisation are also putting greater pressures on wastewater recycling, and the intensification of treatment, required to avoid potential harm to the increasingly vulnerable ecosystem, will also rise.
With these pressures, the increasing real costs will be passed on to the industry: raw material (water), distribution, recycling, production (water treatment), and redistribution. To date only part of this cost was recovered from industries. Capital investment on water infrastructure and treatment processes due to increased demand will also be passed on to industries. Moreover, the principle of ‘polluter pays’ is already becoming the norm internationally and countries are already considering surcharges on wastewater that will be daunting for industry. Companies that maintain the status quo and don’t address these emerging issues will find themselves in a financially untenable position, particularly those who are water-intensive industries such as pharmaceuticals, food & beverage, electronics, leisure, alcohol and manufacturing. The solution lies in innovation, and the most cost-effective and efficient way to innovate in water management is to have experts on hand. We all endeavour to remain ahead of the curve in our chosen core area of expertise, and the water sector is no different. Keeping on top of developments in water infrastructure and technology will becoming increasingly important. Water infrastructure is ageing and there has been a significant investment gap in recent decades. Companies will have two choices: ignore these inevitable changes in the industrial landscape and invest millions of pounds or euros to upgrade their infrastructure, or take timely action to outsource and bring in sectoral experts in water treatment. Those who take the latter route will benefit from utilising the latest technology and resources provided by their water management partner.
With water becoming more expensive, the impetus to recycle water is increasing. Moreover, raw materials used in production processes often escape in wastewater in large quantities. On average, industrial companies that we have engaged with in the past have been able to reduce their water use and production of wastewater by around 40%. But the benefits of recycling water and reducing wastewater go far beyond the financial. Pressures on the availability of water and extreme weather events will also lead to increasing water security issues. We have worked with industrial companies to provide water recycling solutions which have resulted in near selfsufficiency on sites. This also cuts costs in the transportation of water, which in large quantities is more significant than oil, gas and electricity. The obligations to liaise with environmental regulators increases year on year, and it will become critical to have a partner that can lead in this conversation. Outsourcing also brings with it the benefit of specialist human resources and knowledge on best practices. Then there are the other usual benefits commonly associated with outsourcing such as mitigating risk in the operation of assets, minimising fixed costs and utilising technical support services. In the short to medium term, outsourcing your water management will simply be a competitive advantage and an easier way for pharmaceutical manufacturers to ensure compliance with new legal obligations coming into force. But in the long-term, with increased pressure on water systems and the need to keep up with technology, it will become a financial necessity.
ma Ache 8 5, 201 11 â€“ 1 e n n i u a J M , rt am u f k n a Fr any Germ .1, hall 3 n i s u Visit C71 booth ward ok for o l e W u! ing yo to see
Production level 4.0 Excitement level 100 % www.boschpackaging.com
With Industry 4.0 solutions from Bosch Packaging Technology, the connected factory is already reality. Thanks to intelligent solutions at machine level, overarching software, and data-based services, new potentials for increased quality, productivity, and efficiency open up. Bring your food and pharmaceutical production to a new level. Processing. Packaging. Excitement.
As the deadline approaches for companies to be compliant with the new legislation to apply serialisation codes to every applicable pack of product, Gill Wright, design & development director, Cirrus, asks if you are ready for FMD…
THE CLOCK IS TICKING T
he Falsified Medicines Directive (FMD) 2011/62/EU, which is due for adoption in February 2019, will require pharmaceutical companies to apply serialisation codes to every applicable pack (OTC and some minor exemptions). As a consequence, artwork changes will be required, which all too often are treated as a rushed after-thought. The World Health Organisation (WHO) estimates that around 50% of product recalls are still attributed to artwork errors and mislabelling. The industry’s ‘speed to market’ requirements have put more pressure on artwork teams across all aspects of the supply chain to deliver ‘right first time’ and ‘on-time’ for critical product launches. However, it is essential that all brand-owners consider the required changes in good time. Pharmaceutical artwork is a specialist market and artwork creation is often complex so selecting an experienced partner can prevent damaging hard-earned reputations or even product recall. The impending legislation will affect all prescription medicines for the European market. The first step to comply with this legislation is to get your artwork amended and approved. WHAT WILL CHANGE? The legislation requires a ‘unique identifier’ to be placed on product/ packaging so it offers full traceability throughout the supply chain. This takes the form of a data matrix code,
a randomly generated serial number as well as a national reimbursement number, if present, and batch and expiry dates. It can’t be too hard to add these extra codes to an existing pack – can it? The addition of a new code is relatively simple but creating the required space and its impact on the pack’s overall design is often more involved than imagined. As well as an area for the code, it will also require a surrounding ‘Quiet Zone’ that further reduces the availability of free space. In the past, this panel on the pack only needed to incorporate a batch code and expiry stamp so the additional code may force text to move onto another panel. As the pack’s graphics are reformatted it is essential that compliance with other existing legislation is not overlooked. The inclusion of the proprietary name, generic name and dosage to appear on three opposing faces also needs to be taken into consideration. The FMD also requires a brand-owner to add a tamper-evident feature to their packaging which can have a significant impact on a pack’s realestate. Tamper evident labels require varnish and text free space so this adds further pressure on already busy pack designs. If the brand-owner decides not to use a tamper-evident label, a mechanical or constructional solution is another option. However in order to achieve this, particularly if the brand-owner is already using a standard reverse tuck-end carton, it may force a move to another carton
format, such as a skillet-glued, to further increase available space. IT’S HERE TO STAY Whatever anyone thinks, Brexit won’t stop the UK implementation of the Falsified Medicines Directive as it was passed into UK law in 2013. Furthermore, the UK Government is being urged to comply with EU legislation to ensure harmonization and avoiding disruptive supply chain issues across Europe. [However, for UK companies, the EMA’s relocation to mainland Europe could have a potential impact leading to another tranche of artwork changes for centrally registered products. The outcome is still unfolding and not yet clear although it is likely will mean a change of MA holder address for centrally licensed products. A CHANGING SUPPLY LANDSCAPE It was previously commonplace for un-audited ‘local’ suppliers to produce market specific artwork, with no asset control of artwork files and even less control if the process was global. The associated risks for error and for non-compliance were high in this scenario. A typical ‘big pharma’ organisation, even today, would have multiple vendors, some compliant and some not. The market is seeing a significant shift to control artwork lifecycle changes and new product launches via a truly complaint artwork partner.
In order to comply with the new directive it is essential to allow adequate time for potentially signiﬁcant artwork changes.
WHY DO THINGS STILL GO WRONG? In order to comply with the new directive it is essential to allow adequate time for potentially significant artwork changes. The pressure to get compliant products quickly into the marketplace can impact on the quality of the artwork brief. This inevitably results in more artwork cycles due to errors and omissions whilst further extending lead-times and escalating costs. The issues can be numerous and largely stem from a lack of understanding of what’s required. In order to develop the right artwork briefs, it’s essential to build a partnership that is set-up for success with both parties working to get the best output. Leading artwork providers will be dealing with many different customers, with 1000s of artwork requests, all with differing needs and requirements. All customers are different and an agency will need to be sure it is delivering exactly what’s required.
SELECTING THE RIGHT ARTWORK PARTNER Pharmaceutical artwork is a specialist market and any supplier’s workﬂow should be compliant with PS9000/ ISO9001, audited and dedicated to providing an artwork service. A supplier’s artwork systems should fit in with your own ways of working and they should have enough capacity to deal with these changes in addition to regular artwork lifecycle tasks. There should also be a clear understanding that the approved artwork file should not require any further manipulation by the print vendor so there are no touch-points in the process. The use of an automated workﬂow will significantly reduce the potential of any errors. Non-compliance will put both supply and sales at risk. Remember, the clock is ticking… February 2019 isn’t that far away.
Glass primary packaging
Customizable solutions for parenteral drugs
High-value sensitive injectables
Best-in-class for biologics
Analytical and clinical tests
CMO / CRO
Fill & ďŹ nish
EZ-guide Facility solutions
From freeze drying, process & analytical equipment to independent R&D consultancy and Iyo-lab analysis or training courses Exclusively offering Penntech advanced aseptic liquid filling machines
In this article, John Johnson, vice president, Pharma Biotech, NSF International, looks at the revision to Annex 1 and the important questions steriles manufacturers and pharma suppliers should be asking themselves.
ASKING THE RIGHT QUESTIONS R
egardless of the dosage form you supply, whenever the EudraLex Volume IV GMP regulations are revised, it is important to take in the wider picture. With the introduction of a significant revision to Annex 1: Manufacture of Sterile Medicinal Products, licence holders and pharma suppliers should ask themselves:
Why is the regulation being changed?
How will it affect my operation or company as a whole?
Does the revision signal a change in perspective within EMA?
Does the revision imply how changes will be monitored and enforced?
What do I need to do to keep in step with these changes?
Failing to answer these questions, specific to your organisation, is like driving in the dark at breakneck speed without your headlamps on. Whilst Annex 1 is focused on sterile production, the clarifications and changes will have a definite knock-on impact on how the regulators regulate and how the industry designs, operates and checks the effectiveness of the whole pharmaceutical quality system (PQS).
In order to comply with the new directive it is essential to allow adequate time for potentially signiﬁcant artwork changes.
It is therefore important to examine the reasons for the revision to Annex 1 and ask yourself some key questions: KEY REASONS FOR REVISION TO ANNEX 1 1. New technologies require new regulations to clarify the GMPs.
2. The EU competent authorities are concerned about the pressures within the PQS — especially regarding a perception of higher staff turnover, heightened commercial pressures and projects that run late or are out of control. The authorities believe clearer regulations will help industry improve GMP compliance.
QUESTIONS TO ASK • Does my organisation utilise unique or innovative production, facility or QC technology? How would I present the scientific justification for that technology? How does it work? What happens when it doesn’t work? How could I check its ability to ensure critical product quality attributes are met now and in the long-term? • Does my staff turnover within the critical position holder group exceed 15% per year? Am I losing my best people to other employers? How should I retain the high performers? • How well does my organisation introduce new products? Do we only introduce materials and drug products appropriate to the facility and the current quality system?
3. The authorities are troubled by recurring GMP deficiencies, basic defaults against the regulations, inadequate root cause analysis, ineffective CAPA and poor deployment of ICH Q9 Quality Risk Management. Issues concerning sterility assurance are not diminishing, causing recalls and product shortages. When trust is eroded, there is a greater need for verification and enforcement.
• Does my PQS have a clear risk management process that leads to a risk register, acted on via annual quality objectives? • Does my product impact assessment process justify unsound, unscientific or bad practices, or continue supplying product without addressing root cause? • Am I noticing recurring issues? Do I actively seek to reduce the severity and frequency of recurrence?
4. The authorities see a trend in fragmented supply chains leading to the diffusion of QA oversight and responsibility. Sterile products are often made in locations and by companies without a long-compliance history in this field with low-level understanding of the technologies and risks. This is evidenced by the prevalence of basic GMP deficiencies noted on-site during regulatory inspections. Therefore, Annex 1 needed to be made less ambiguous with less room for interpretation.
• How do my EU Qualified Persons oversee the supply chain as required by Annex 16, and how is this documented? • How well does my vendor approval system work and is a person-in-plant is needed to guide and verify our contractor’s performance? • Do my manufacturing partners operate a quality system that meets ICH Q10 and is used in day-to-day operations?
5. After the global recession 10 years ago, many firms slashed their training budgets and how they educate their staff and develop their managers. Some critical position holders may have the ‘know-how’ but not the ‘know-why’, hence the trend in sterile inspections for poor decision making, inadequately completed investigation reports and acceptance of repeat, low-level issues. More detail is needed in Annex 1 to provide clearer guidance and direction.
• Do we educate staff, so they can make the right calls at the right time? Are our training programmes developing the subject matter experts of the future? • Do we have a successor programme? • Do we define ‘station manning’ to allow people to shadow managers so they learn as part of their daily job? • How do we check that training has been absorbed and best practice is implemented?
So, whether or not you are a steriles manufacturer, take time to formulate an action plan. Your EU regulator is telling you: ●
Better regulation is needed as many sectors are struggling to comply with the basic GMP requirements.
Product shortages, recalls and regulatory censure are troubling and demonstrate that changes across the industry in the last 10–15 years are not visibly improving the quality or safety of products manufactured or supplied in and to global markets.
Recurring GMP deviations and deficiencies demonstrate a lack of effective root cause analysis, a lack of rigor in identifying the right CAPA and an acceptance of variation that can significantly impact product quality.
Though a quality system (underpinned by a robust staff education program) is a mandatory requirement, it will not deliver the required level of quality assurance without the engagement of staff at all levels.
QUESTIONS TO ASK WHEN ANY GMP REGULATION IS REVISED… What investment do I need to ensure long-term, sustainable compliance to this requirement? How does the revision aﬀect my current facilities, utilities and equipment? Do I need support to make this change eﬀective, timely and long-term? Do we need a behavioural or cultural change, and how can we equip our team to manage this change professionally? Why didn’t our organisation know about this change earlier, so we had more time to respond in a timely, controlled manner? Who needs to know about this, where can I get the details and how can they be shared with the wider team? Does my organisation comply with the new regulations, how should I respond and what do I need in place to enact a timely GMP remediation plan ahead of a crisis or the next regulatory inspection? What policies, procedures, logbooks, records and batch manufacturing documents are aﬀected by this change?
EVOLVING PHARMA. BY YOUR SIDE. ACHEMA 2018 | HALL 3.0 - STAND F49 www.ima.it
Missing a trick? Even though technology is transforming many areas of our everyday lives, the pharmaceutical sector is still proving slow at adopting major digital and brand trends. Here, Vicki Young, CEO & founder of Nalla, highlights four trends being embraced by others as a useful starting point.
e’re all aware that technology is transforming every area of our lives, from our working environment, to planning our social lives, shopping for groceries, exercising, and even ﬁnding the loves of our lives. For almost any aspect of your daily life there’s some technology on oﬀer designed to improve the experience. Consumers have adapted to this digitally enhanced routine with the greatest of ease. We’ve become as expectant of technological assistance, or enhancement, as if it’s a sort of birthright. So, why wouldn’t we expect to have our experience of healthcare improved by technology? The problem is, we do, but it’s not there yet…
1. World Internet Users Statistics and 2016 World Population Stats: https:// www.internetworldstats. com/stats.htm
From our work within the pharmaceutical sector (including pharma-tech), we’ve noticed the sector is slow to implement major digital and brand trends embraced by others. We thought we’d highlight some of them here as a useful reference. Many of them are easily implemented internally. However, some may require external support to achieve.
1. YOU HAVE MORE THAN ONE AUDIENCE
2. GET OUT AHEAD OF THE CONVERSATION
3. WE’RE NOT ALL DIGITAL NATIVES
The pharmaceutical sector is not unique in its need to address multiple audiences. Primarily the customers are: (a) Consumers (patients) (b) Healthcare providers
As of June 2017, 51% of the world's population has access to the Internet.1 The internet however is both a benefit and a bind for the pharmaceutical sector. Often, information found online about therapies and medicines can be, at best, irrelevant to large numbers of consumers, or at worst, wholly inaccurate/misleading. It also means the majority of consumers are no longer limited to buying what’s available on the shelves in their local pharmacy. Nor are they limited to the amount of research they can do on products, or the feedback they can provide.
Although we’re focusing on the rapid adoption of technology for the majority of consumers, we need to also be mindful that, for some consumers and healthcare providers, emerging technologies are not so easy to embrace. Certain audience groups, including many elderly consumers (who incidentally are often those who require more medical needs) can be understandably wary of technology. That’s not to mean they can’t use it, they just perhaps need a bit more support in doing so.
Both of these audiences will have different requirements of your brand, ranging from functional and results-driven reassurances (e.g., safety and risk) for healthcare providers, to the more emotive and real-life reassurances (e.g., impact on family) for consumers. What’s important to note however is that, in most cases, one will inevitably inﬂuence the other as their relationships can often strengthen, and become more dependent upon each other for feedback when serious/long-term illness occurs. Because of this it’s imperative you consider the brand experiences for both audiences. By focusing on the individual expectations/needs of each, you’ll build stronger brand loyalty from both collectively. A quick and simple method to achieve this is to ensure you have dedicated areas on your website that talks directly to each audience. This enables them to access the information that is relevant for them, and provides reassurance that you’re focused on their individual needs.
By taking the time to listen to consumers, understand their needs and connect with them through the technology they use (e.g., SMS, Facetime or Skype), you can create greater long-term engagement and ensure the internet is benefitting your brand, not binding it. Also, by actively managing the ﬂow of information about your brand you can help provide the correct, most relevant information for consumers and, ultimately, take the lead on the conversation.
If a brand is introducing technology to be used by non-digital savvy audiences, it’s their responsibility to design it to be accessible to all. Ensuring the brand design, UX and related comms are as approachable as possible will reassure consumers that you’re there to support them, not exclude them by introducing technology.
If a brand is introducing technology to be used by nondigital savvy audiences, it’s their responsibility to design it to be accessible to all.
4. PUT THE CONSUMER AT THE HEART OF YOUR BRAND STRATEGY When you consider the world’s leading brands, one of the key commonalities between them is that they all know their customers, inside out. They invest heavily in obtaining extraordinary insight into their target markets. With this insight, they create robust brand strategies that directly communicate with their core audiences in relevant and engaging ways. What’s remarkable is that the greater the level of engagement a consumer feels with a brand, the more likely they are to willingly provide more information and insight back to the brand. For those of us who don’t have the budgets, or the reach of the likes of Apple and Coca-Cola, you can still manage this by simply putting the consumer at the heart of everything you do. What we mean by that is to consider the consumer wants and needs; how they might receive something, not only at launch but right from the product development stage. From name and brand identities, through to press releases and how to navigate your website — everything should be designed with the consumer in mind. Something that resonates deeply with the branding challenges businesses face is a great quote from Maya Angelou — People don’t remember what you say or do, they remember how you make them feel.
Breaking new ground Here, Steve Lyon, digital lead, Communities & Content, Allied Market Research (AMR), discusses some examples of new technology in the antibody conjugate drug space and the ground-breaking potential this new class of drugs will have in the treatment of cancer.
n pursuit of more targeted therapies and clinically effective drugs, pharmaceutical companies are increasing their research and development activities in biologics. Although a majority of this work is focused on monoclonal antibodies (mAbs) and recombinant proteins, progress is being made in specialised drugs. Antibody drug conjugates (ADCs) are a new class of drugs that are gaining attention from both large and small pharmaceutical companies as they offer promise in cancer therapeutics. They consist of an mAb — an antibody that is specific to the target associated antigen, a cytotoxic drug - designed to kill target cancer cells, and a linker — that attaches the cytotoxic agent to the antibody. Thus, antibody drug conjugates combine the targeting ability of a monoclonal antibody and the target specific cell killing ability of cytotoxic drugs. The market for antibody drug conjugates is witnessing fast growth, which is supported by the advancement in medical technology, the rise in the occurrence of cancer cases worldwide, growing ageing population, and the growing obese population. Furthermore, the increased research activities on antibody therapies, advanced drug discoveries and oncology diseases as well as the growing
collaboration between research institutes are propelling the growth of the industry. Nonetheless, the high cost of the procedures and the lack of fund pose a threat to the growth of the ADC market. According to a report published by Allied Market Research, the antibody drug conjugates market is expected to reach $3,198 million by 2023, registering a CAGR of 12.9% from 2017 to 2023. Companies within the space are coming up with superior technologies to develop more effective and efficient antibody drug conjugates. For instance, ADC Therapeutics, a developer of proprietary PBD-based antibody drug conjugates, recently announced that it would deliver its presentations regarding strong preclinical data for its two new investigational programmes ADCT-601 targeting AXL and ADCT-701 targeting DLK-1 at the American Association for Cancer Research (AACR) Annual Meeting. Daiichi Sankyo, a global pharmaceutical company announced that its HER2-targeting antibody drug conjugate (ADC) received SAKIGAKE Designation for the treatment of gastric cancer by the Japan Ministry of Health, Labor and Welfare (MHLW). Synaffix, a Netherlands-based biotech company announced the launch of a new platform of highly
potent cytotoxic ADC payloads that integrates into its existing ADC platform. ADC THERAPEUTICS PRESENTED TWO NOVEL ADCS In April 2018, ADC Therapeutics announced its presentation regarding strong preclinical data for its two new investigational programmes ADCT-601 targeting AXL and ADCT-701 targeting DLK-1 at the American Association for Cancer Research (AACR) Annual Meeting which took place from 14–18 April 2018 in Chicago, USA. Dr Jay Feingold, chief medical officer and senior vice president of Clinical Development at ADCT said: “Our two new investigational programs show compelling efficacy and safety in preclinical studies. These results provide an important step to advance ADCT-601 and ADCT-701 into the clinic and enlarge our pipeline of PBD-based ADCs in multiple
ongoing clinical trials for the treatment of both solid and haematological cancers.” Highlights of the data to be presented are available on the AACR conference website — www.aacr.org DAIICHI SANKYO'S HER2TARGETING ANTIBODY DRUG CONJUGATE RECEIVED SAKIGAKE DESIGNATION FOR GASTRIC CANCER In March 2018, Daiichi Sankyo announced that DS-8201, an HER2-targeting antibody drug conjugate (ADC) received SAKIGAKE designation for the treatment of HER2positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labor and Welfare (MHLW). The company said that it intends to work closely with the Japan MHLW under the terms of the SAKIGAKE programme to speed up the development of DS-8201 since Japan has one of the highest cases of gastric cancer worldwide. The SAKIGAKE designation system fosters R&D in Japan, propelling early practical application for novel pharmaceutical products, medical devices and regenerative medicines. As a designated medicine under the system, DS-8201 has
prioritised consultation, a dedicated review system to support the development and review process, and a reduced review time. SYNAFFIX LAUNCHED TOXSYN, A NEW PLATFORM OF ADC PAYLOADS Synaffix BV, a biotechnology company announced the launch of a new platform of cytotoxic ADC payloads that integrates into its current ADC platform. With the launch, the company becomes a provider of technologies needed to quickly translate antibodies into proprietary ADC products. The new toxSYN platform comprises four highly potent payloads offering multiple mechanisms of action and a way for commercialisation when integrated with the components of Synaffix’s GlycoConnect and HydraSpace technologies. Validated clinically with well-known efficacy and safety profiles, the payloads were selected to address the two types of biologies that exist across ADC targets such as rapidly-dividing cancer cells and quiescent cells. “We expect this important expansion of our ADC technology to further advance our internal research and facilitate collaborations with a much broader set of companies,” said Peter van de Sande, CEO of Synaffix. “By providing these four distinct payloads through our new toxSYN platform, we can now enable any company with an existing antibody to rapidly establish a highly-competitive clinical-stage ADC programme for its own development pipeline.”
The market for antibody drug conjugates is witnessing fast growth, which is supported by the advancement in medical technology, the rise in the occurrence of cancer cases worldwide, growing ageing population, and the growing obese population.
All New QTRamâ„˘ Portable Raman System for Content and Blend Uniformity Nondestructive quantitative transmission Raman analysis of solid dosage forms over a large sample volume. No sample preparation, no solvents, with results in seconds. +1-302-368-7824
Learn More About the QTRam www.bwtek.com/NewQTRam
In the genes Here, Tony Hitchcock, technical director at Cobra Biologics and Joanne Anderson, business development director at Symbiosis, whose respective companies were recently awarded a 16-month collaborative grant of £1.9 million from Innovate UK, discuss the challenges associated with manufacturing for gene therapies.
hey are cited by many as a ‘medical revolution’. Emerging gene and cell therapies to treat everything from cancer to haemophilia and blindness are being hailed as huge successes. Such ground-breaking therapies do not come without risk, however. The use of gene-based medicine remains nascent; costs are high, timeframes are tight and quality standards are strict. Nevertheless, the Association of the British Pharmaceutical Industry (ABPI) estimates the global cell and gene therapy market will be worth up to $21 billion annually by 2025. NEW THERAPIES, NEW GROUND Pharmaceutical and biotechnology companies are now racing to develop or acquire assets to develop these life-changing and life-saving therapies, many of which are commanding some of the highest prices ever seen for a medicine. Due to the potential life-saving qualities of such therapies, clinical development programmes for innovative gene therapies have been actively accelerated by regulatory bodies such as the FDA and the EMA by the application of a ‘priority review’ or ‘breakthrough designation’ status, seeking to expedite widespread access to these new medicines.
The delivery vehicle that underpins many of the in-development cell and gene therapies and specifically those recently launched such as Yescarta and Kymriah, is a viral vector. Viral vectors are tools used to deliver genetic material into cells. Due to the pharmaceutical industry and regulatory bodies drive to get treatments to patients quickly, the speedy and adaptable production of viral vectors from companies like Cobra Biologics and Symbiosis is paramount. The manufacturing challenge is quite unique. The handling and processing of such complex and delicate products like viral vectors needs specialist skills and expertise to create an integrated supply chain to minimise risk. In addition, costs are huge. Gram per gram, viral vectors are quite possibly the most valuable raw materials on the planet. These are ground-breaking treatments. They don’t fit the normal criteria for conventional drug development and aren’t following typical timelines. The speed such products are moving through clinical development compared to classical biologics is creating a new paradigm, at three to four years for a vector versus eight to 12 years development is happening at breakneck speed. In reality, those involved in the supply
26 chain are in fact setting the precedent for future manufacturing processes and strategies. CHALLENGES IN THE PROCESS Whilst accelerated pathways are a positive for patients in the long run, shortened timelines for the manufacture of viral vectors make it more difficult to develop commercial manufacturing processes that can produce vectors at the right quality, in the required amounts, and at costs that are reasonable enough to secure reimbursement from healthcare providers while still making financial sense to the developer. From a processing perspective they pose a number of challenges: firstly, in terms of size, they are 12 times the diameter of mAbs with diameters up to 120 nm and are processed at concentration in the region of pg to µg/L — compared to proteins processed at 10’s–100g/L levels, secondly the products are often highly labile and have poor thermal, physical and chemical stability. The consequence to this is that from a technical perspective these products pose a significant challenge not only in the manufacturing of the active drug substance, but also during the production of the drug product to minimise product loss not least through 0.2 µm filtration steps but also during process manipulation steps can damage viral capsids and result in the loss of infectivity and functionality.
There is also an ethical challenge; many of these products are life savers and have hugely transformative impacts on patient’s lives so are the development programmes being rapidly accelerated towards clinical licensing to allow patient access to successful products? To achieve this, timelines and opportunities to develop and optimise manufacturing processes are at a premium. Consequently, there is a need for coordination between all parties in the supply chain to work together to ensure material supply during both clinical development phases and for licensed products whilst ensuring that all required safety and regulatory guidelines are met throughout. Ultimately, if mistakes happen they will be very costly on all levels. Products will not reach patients, many with terminal illnesses and for whom time is of the essence.
Projects such as those ongoing at Cobra Biologics and Symbiosis’ will support a larger investment in the production capabilities of both companies, streamlining and de-risking the manufacturing of viral vector products through operational and commercial alignment. The resulting supply chain offering will help realisation of the clinical and commercial ambitions of drug developers, leading to more innovative gene and immunotherapy medicines reaching patients. Moving forwards, we expect the massive impetus to get products to patients to continue to grow. The manufacturing path is not well trodden yet, it remains somewhat of a learning curve for all those involved, but as many of us are now working together to resolve manufacturing problems we expect the future of cell and gene therapies to be just as ‘revolutionary’ as predicted.
THE FUTURE Gene and cell therapies are a huge opportunity, with potentially lifechanging consequences for millions of patients across the world. As discussed, developing these therapies is not without challenges, but the industry has so far responded to these swiftly with the expertise needed to manage such specific demands.
Gene and cell therapies are a huge opportunity, with potentially lifechanging consequences for millions of patients across the world.
The handling of recombinant vectors also poses specific concerns with regards to biological containment and segregation from other products and the ability to remove these types of products from the facility also pose specific requirements in terms of operational expertise. Consequently, drug developers are heavily reliant upon specialist providers for the production of drug substance and drug product.
ACHEMA 2018 11-15 JUNE
FRANKFURT am MAIN - GERMANY
HALL 3.0 - STAND A24
JOIN US AS WE UNVEIL THE NEXT GENERATION OF THE ACCELA-COTA®, THE ALL NEW THOMAS ACCELA-COTA® PRO.
WORLD’S MOST ADVANCED TABLET COATING SYSTEMS & TABLET PRESS TOOLING THOMAS ENGINEERING INC. - 575 West Central Rd. Hoffman Estates, IL, 60192 USA - firstname.lastname@example.org - tel. +1-847-736-8975
SOLID DOSE SOLUTIONS
Taking the holistic approachâ€Ś â€Śto solid dose solutions. Here, Pingyun (P.Y.) Chen, PhD, director of Early Development at Catalent Pharma Solutions, details some of the important considerations required in product development and how a holistic approach can help save money and time in the long run.
rystalline forms predominate in solid form screening, although more recently, the traditional salt and polymorphic forms have been supplemented by co-crystals and amorphous solid dispersions. The aim is to select the solid form with optimal solubility, stability and manufacturability, and balance those factors with cost and material availability to ensure projected timelines are met. A phase-appropriate strategy to solid form screening is now common. This iterative process involves increasingly comprehensive screening activities being applied as material becomes available and technical demands alter. In the initial stages of development, speed is most important, so limited screens are used to identify a solid form that permits progression. Later, more material is available and speed is less critical, so more comprehensive screens may be employed to identify all solid forms to enable broad patent protection, and select the best of these for commercialisation. The growing number of poorly soluble molecules in the development pipeline highlights the importance of choosing a solid form that will improve solubility and bioavailability. A successful salt form can even remove the need for more complex and expensive formulation techniques. A carefully planned strategy,
employing automated screening technologies, can save both time and money. SCREENING STRATEGIES The starting point of the screen is the collation of data on its physiochemical properties, including solubility in aqueous buffers and in bio-relevant media. The solubility, permeability and projected doses are used to evaluate if solubility and dissolution rate will limit drug absorption. These provide the basis of solid form screening and formulation strategies, including any bioavailability enhancement that might be required. Crystallisation is the preferred method for isolating and purifying the API, as it is cheaper and more effective compared to other methods, especially on larger scales. Only small quantities of API are required for crystallisation screening, which will be done with a variety of solvents and conditions. This can be carried out as part of a salt screening to create a more soluble form, if the API has ionisable groups. Soluble salts have further benefits, including less pharmacokinetic variability, increased exposure and simpler formulations. However, solubility is not the only consideration, dissolution and precipitation
kinetics in biorelevant media will also be required. More recently, the potential of co-crystals in drug formulation has become apparent. These multicomponent crystals combine an API or its salt form with at least one other neutral co-former molecule. They allow the crystal structure to be modified, and thus the APIâ€™s properties to be optimised. The screening process is similar, but as the molecular interactions between the API and the coformer are not as strong as the ionic bonds in salts, specialised techniques such as solvent-drop grinding must be applied. This limits its applicability to early stage development. While some are easy to find, the process for scaling up a co-crystallisation is more challenging than for a simple salt, but as experience grows, this should change. Some molecules are polymorphic, existing in more than one crystalline form. These will have different physical properties, including solubility, stability and bulk density. Where this is the case, it is important to ascertain which is the most suitable and stable for development. Polymorph screening is required to ensure process reliability and patient
safety. This should look at those parameters that may inďŹ‚uence the formation of different forms, and whether processes such as micronisation or wet granulation might induce a polymorph change. If a compound is particularly insoluble, then an amorphous solid dispersion may be most appropriate. Screening can be used to find more soluble dispersions, which will typically be twoâ€“1000-fold more soluble than the crystalline form, depending on its lattice energy and the presence of hydrogen bonding capability. Polymers and surfactants can be added to give further enhancements. These dispersions can be prepared by techniques including the fast evaporation, freeze drying or spray drying of solutions, or by hot melt extrusion. DELIVERY CONSIDERATIONS Administration route, dose, dosage form and release profile also need to be considered at the outset. A salt may be optimal for oral delivery, but the uncharged active may be better for topical application. For an oral dose, the crucial factors include stability, solubility and dissolution rate, compatibility with excipients, bulk density and compressibility. If a drug crystallises quickly and is likely to precipitate in vivo then excipients to inhibit crystallisation should be added.
Excipient and device compatibility are critical for inhaled formulations, along with hygroscopicity and milling. For solution formulations, solubility and stability in the solvent are important, as is the pH of the solution. FROM DISCOVERY TO DEVELOPMENT The transition between discovery and development is rarely as smooth and efficient as it might be. The candidate molecule created by medicinal chemists should have good selectivity and potency, but is unlikely to have been designed with development and drug delivery in mind. This disconnect is at the heart of the current issues with suboptimal physicochemical and biopharmaceutical properties.
considerations when deciding on a salt form are ease of synthesis and cost of goods, rather than the properties that will be required for optimal downstream processing and formulation. Changes get more challenging and expensive to make as the development process proceeds, with many steps having to be repeated. This extends timelines and escalates costs. It is therefore vital to consider how a molecule will be developed at the outset. If the best option can be identified at a very early stage, it will save costs, prevent repeated re-working of steps of the development process, and ensure that effective, safe drugs reach patients as early as possible.
Engagement with preformulation and formulation scientists during the lead optimisation process is a key step in designing a developable molecule. All too often, the formulation scientists are brought into the process after the molecule and salt form have been determined, which is too late. Instead of addressing the different problems in the development process holistically, they are more likely to be considered sequentially. The predominant
The transition between discovery and development is rarely as smooth and eďŹƒcient as it might be.
SOLID DOSE SOLUTIONS
Keep it dry David O’Connell, director Pharmaceutical Development at PCI Pharma Services discusses the advantages of dry granulation as an alternative to traditional wet granulation for the development and manufacturing of solid oral dosage forms, including tablets and capsules.
Q: WHAT EXACTLY IS ROLLER COMPACTION? A: Roller compaction is a form of dry granulation, through the aggregation and densification of dry powders into a uniform solid mass (ribbon). The ribbon is then broken down into specific granule size via a milling system, which means that the powder particles are made to adhere to each other to form the larger multi-particulate units — the granules. Granulation can be performed without the addition of a liquid, so called ‘dry granulation’, which differs from a ‘wet granulation’ method, such as high shear granulation or ﬂuidised bed granulation. In summary, with a dry granulation method, the powder blend is compacted by applying a force onto the powder, generally increasing the size of the granule. Q: SO HOW DOES THIS FORM OF DRY GRANULATION WORK? A: Dry granulation works by feeding a powder blend via gravity or feeding system to a set of directly opposed, rotating rollers. The powder is fed into a decreasing gap diameter between the rollers. The gap between the rollers is controlled, and the powder is subjected to high pressure or force — so it is designed to increase the bulk density, as well as the uniformity of the granule itself. The pressure applied and the gap diameters are the most important parameters in this dry granulation process.
Q: WHY IS THE PRESSURE OR FORCE APPLIED SO IMPORTANT? A: The powder is fed into the rollers via frictional forces — depending on the amount of powder, the gap diameter and the given force, the powder will be ‘compacted’ into a predefined ribbon thickness. To ensure the end result of equal granule properties, a precise process control is critical, and this is determined by the pressure at which the powder is forced through the rollers — hence its importance. Q: DOES ROLLER COMPACTION OFFER ANY BENEFITS OVER WET GRANULATION? A: It does and this really depends on the compound itself. If you have, for example, a moisturesensitive compound, wet granulation could prove either very difficult or impossible in terms of inducing potentially toxic impurities. In contrast, the roller compaction process does not need the addition of a liquid binder and therefore provides a more suitable granulation process. In addition, there is no drying stage with roller compaction and so if you have a compound that either has a low melting point, or is sensitive to heat, again wet granulation with drying would not be appropriate — whereas roller compaction would offer a
more suitable option. With the addition of no drying stage, it delivers a more efficient means of processing, with less time to produce granules, and in theory, it can be a continuous batch process with a suitable feeding system. Q: DO OTHER FORMS OF DRY GRANULATION EXIST? A: Yes, an alternative method of dry granulation would be slugging — when a tablet press is used for the compaction of a large compact, which is then subjected to milling, prior to further processing. However, this may cause some inherent challenges. For example, materials with low bulk density and small particle sizes generally do not ﬂow well into the die of a tablet press, which potentially leads to differences from one tablet (or ‘slug’) to the next, causing ﬂuctuations in the forces applied to the individual tablets or slugs. This would then lead to differences in the mechanical strength, causing issues with the milling of the slugs and the granulate properties. Q: DO DIFFERENT TYPES OF ROLLER COMPACTION EXIST? A: Yes, there are two main categories, the first being where the gap between the rollers is fixed, the second is where the gap can be changed depending on the amount of powder introduced, which is described as ‘ﬂoating’.
SOLID DOSE SOLUTIONS
…with a dry granulation method, the powder blend is compacted by applying a force onto the powder, generally increasing the size of the granule Q: DOES ONE OFFER ANY ADVANTAGE OVER THE OTHER? A: Consensus opinion does seem to think there is an advantage to the ‘ﬂoating’ option. If a fixed gap option is used, it can mean inconsistency in terms of the amount of powder that is drawn into the compaction area, leading to differing forces being applied to the powder bed. As in the case of slugging, this in turn would lead to ﬂuctuations in the ribbon and granulate. However, by using technology offering a ﬂoating gap option, such as GERTEIS, the distance between the rollers will change according to the amount of powder provided and the force applied. This then remains constant, ensuring that ﬂuctuations in the granules are minimised — resulting in a more uniform or homogenous granulate. Q: SO, WHAT HAPPENS FOLLOWING THE GRANULATION STAGE? A: Firstly, dry granulation using roller compaction technology is a continuous process if using integrated technology — which differs to that for wet granulation. Following compaction, the resulting ribbons are then milled immediately, using a screen with a set mesh size to limit the upper particle size. It is also worth stating here that milling should be as gentle as possible to avoid
creating fines within the resulting granulate, as the overall process minimises ﬂuctuations in the granules. The resulting granulate can then be further processed into either a tablet or capsule dosage form with increased confidence of dose uniformity. Q: HOW DOES DRY GRANULATION IN THE FORM OF ROLLER COMPACTION OFFER ADVANTAGES WITHIN THE ARENA OF PERSONALISED MEDICINES, WHICH ARE BECOMING MORE PREVALENT? A: Any compound that has been classified as potent requires specialist handling. Traditional techniques relying on personal protective equipment (PPE) are being replaced, through best and advised practice, with the use of contained engineering solutions to ensure the highest standards of safety and operator protection. With this in mind, identification of a solution able to offer fully contained roller compaction should form part of any decision process — whether you are looking to outsource to a CDMO, or build internal capabilities. Such technologies do exist and are becoming more commonplace. As an example, we at PCI made a decision to invest in a fully contained roller compaction
solution in response to the increase in the highly potent development landscape. However, within the first 12 months of opening the facility, a number of customers approached us specifically requesting dry granulation for very potent molecules, due to the compounds being sensitive to either heat and/or moisture. We therefore decided to install a fully contained roller compactor to address this growing need, allowing us to process molecules with an occupational exposure limit (OEL) as low as 0.01 µg/m3 within contained technological solutions. As a result of the success of this contained facility, we continued with this strategy for any new technologies we were looking to introduce and built the area of the site to house the roller compaction suite to the same standards. This ensured that from a customer perspective, we were able to offer parity between both wet and dry granulation solutions.
Stopper Processing Equipment Taking care of your stoppers from A to Z Pre-treatment handling Washing & siliconization process Sterilization & drying process Sterile delivery
New SPE Series Completely integrated all in one solution Different types of components used in sterile filling: stoppers, plungers, tip caps/needle shields, lined seals, aluminium caps and seals.
Discover more on: www.steelcospa.com/pharma
Join with us at the ACHEMA Frankfurt am Main, 11-15 June 2018
Right royal winners It’s that time of year again when we ﬁnd out who has been given the prestigious Queen’s Awards for Enterprise for outstanding achievements in four main categories. This year has seen a record number of those granted for international trade, here, we highlight a few of the winners from this category… OPTIMISING DRUG DEVELOPMENT Specialist drug development consultancy, Artemida Pharma, has been announced as one of the winners within the international trade category for this year’s awards. “To celebrate our four-year milestone with an award as prestigious as the Queen's Award for Enterprise is a real honour and a testament to how far Artemida has come in such a short period of time driven by the extensive experience of our consultants,” reﬂected founder and managing partner, Dr Sarah Arbe-Barnes. Dr Robert Miller, chief medical officer and managing partner, added: “This award will further encourage us to extend our high standard of expertise in the challenging arena of drug development to our international clients.” OVERSEAS GROWTH GIS has been recognised with a Queen’s Award for Enterprise in international trade in recognition of its growth in overseas markets for the second time. IMAGES TOP TO BOTTOM: GIS Elucigene Diagnostics Lattimer Hanningfield Peli BioThermal
Nick Geddes, CEO of GIS, commented: “We are very honoured to have won a second Queen’s Award — it’s a great tribute to the work done by our skilled and dedicated staff. GIS continues
to grow and ﬂourish — and we are very proud of our track record in exporting our technology across the world.” The company, which exports high performance RIP software, electronics, software drivers and ink delivery system components for industrial inkjet printheads, has seen its overseas earnings more than double in the period 2015– 2017 and now exports to more than 20 countries worldwide. CONTROLLING TEMPERATURE Peli BioThermal, temperaturecontrolled packaging and service solutions provider to the global life sciences industry, has won its second successive Queen’s Award for Enterprise. This year, the company has won in the category of international trade (last year it was a winner in the field of innovation). The judging panel highlighted the company’s ‘outstanding short term growth in overseas sales over the last three years. “We are proud to receive this auspicious award again, this time for international trade,” emphasized Peli BioThermal president David Williams. “It is an absolute honour to receive Royal recognition for our outstanding performance exporting our pioneering products worldwide.”
INCREASING EXPORTS Independent family-owned business that specialises in the design and manufacture of process machinery for the pharmaceutical industry, Hanningfield, has received a Queen’s Award for Enterprise for international trade. The company has achieved growth in overseas sales, with exports representing a significant and increasing proportion of company revenue. Additionally, it has seen a rise in the number of employees at the UK factory, which has been necessary to meet the rise in demand. “I am extremely proud of the team at Hanningfield. Hard work and supreme diligence has enabled the company to ﬂourish on the international arena of commerce,” said Colin Ellis, founder and managing director at Hanningfield. “The industry we are dedicated to supporting has extremely high standards of compliance and quality. Without the dedication and integrity of our workforce to produce excellence we would not be in a position to receive such a high accolade as the Queen’s Awards.” THERMAL PROTECTION SOLUTIONS TP3 Global, innovator and provider of thermal protection for temperature sensitive cargo, has been recognised with the Queen’s
This year has seen a record number of Queen's Awards for Enterprise granted for international trade
Award for Enterprise in international trade for its SilverSkin brand. SilverSkin has become a globallyrecognised brand and is used by many pharmaceutical companies worldwide to help maintain product integrity in transit. “We are extremely proud to achieve the prestigious Queen’s Award for Enterprise for international trade,” commented Clive Wheeldon, president of TP3 Global. “Our commitment to providing marketleading products, innovation and high-quality customer service has resulted in working with the industry’s leading pharmaceutical companies. GLASS PRECISION Glass industry precision engineering business, Lattimer, has secured an award in the category of international trade. Exporting to more than 56 countries worldwide with international orders accounting for 96% of total sales, the company has been recognised for its international sales growth over the past three years. “It is a huge privilege and honour to receive the Queen’s Award for Enterprise,” stated Lattimer Holdings CEO Stephen Waterhouse. “This award is the result of many decades of hard-work and determination. Lattimer has had to evolve and remain resilient since setting up in 1937. It took many years to build a reputation as a solid British
manufacturer before a major breakthrough in the 1970s when we helped a local glass container company solve a problem in their production process. This innovation was so successful it inspired Lattimer to develop other products for the worldwide market.” MEDICAL TECH SUCCESS Medical technology company, Elucigene Diagnostics, has been awarded with the Queen’s Award for Enterprise for outstanding success in international trade. The company’s products are used for the rapid detection of genetic diseases such as cystic fibrosis, and more than 80% of its annual sales come from exports. Over the past two years, the company has witnessed growth in revenues of around 30% and is currently 20% ahead for this financial year. “We are thrilled to have won this most prestigious of awards. Taking a UK-only approach to our sales would not have delivered the strong growth we wanted to see and it is great to be ﬂying the ﬂag for UK life sciences in so many international markets,” said chief executive Dr Mark Street-Docherty. “We have a strong pipeline of new diagnostic products and ambitious plans to expand into new markets, particularly the US, in early 2019, and I hope this award will be well-received by our potential customers and partners in this and other territories.”
First ever truly continuous twin screw Granulator and Dryer on the market QbCon®1 GHPUT THROU OF g/h – 0,5 4 k
Unique Technology for Your R&D • Material flow from raw material to dried granule in a closed continuous operation • Fully automatic cleaning of filter during the drying process • Consistent LOD (Loss On Drying) across all granule sizes • Uniform conveying of the granules from feeding to discharge • Easy scale-up for the development of new products • Continuous application of the granulation liquid by the use of a special pump
– Hall 3.0 –
Booth A 71
Are you curious? We´re going to convince you at Achema!
CASE STUDY: PURIFICATION & FILTRATION
TWO HEADS ARE BETTER THAN ONE Who I Howorth Air Technology & Russell Finex What | Multiple customised solutions for new production facility How | Combination of expertise THE COMPANIES Howorth Air Technology engineers a range of powder containment solutions, aseptic systems and ultra-clean air filtration ventilation systems for medical, pharmaceutical and other industries. Based in the UK with offices in the US and representation in Europe and Asia, Howorth delivers equipment to clients throughout Europe, Asia and the Americas. The company is customer focused, providing bespoke products and turnkey systems to meet the requirements of cleanrooms, operating theatres or pharmaceutical manufacturing facilities. Russell Finex is a global manufacturer of pharmaceutical screening and filtration equipment that supplies equipment to over 140 countries worldwide. The company has offices in the UK, USA, Belgium, India and China, in addition to a network of experience agents and distributors from global locations. THE PROBLEM A leading global pharmaceutical company sought multiple customised solutions as part of a new production facility and had previously held concerns about operator exposure during the processing of APIs, as traditional powder screening machines often do not provide the levels of containment required to ensure operator safety.
THE SOLUTION To tackle this issue, Howorth combined its expertise with those of Russell Finex, and deemd that two systems for pneumatic screening and conveying of pharma powders were required to guarantee containment during sieving in two key production areas. Paul Stanway, business development manager at Howorth Air Technology, revealed: “Firstly, the customer required a DownFlow
Containment Booth, incorporating various process operations such as blending, weighing and sieving. Secondly, a containment isolator, also known as a glove box, was required to sieve and weigh APIs in a fully-contained environment.” Howorth’s WORKSAFE containment booths provide operator protection and are ergonomically and hygienically designed to allow multiple process operations to be carried out. For this specific process, pharmaceutical powders would be pre-weighed, transferred
38 into a hopper then vacuumconveyed into an IBC via a sieving system ensuring the product is screened to guarantee a consistent particle size and remove oversize and foreign contamination. On this occasion, Howorth combined this containment technology with a Russell Compact Airswept Sieve as the integrated powder screening system of choice. This vacuum conveying sieve combines Russell Compact Sieve technology with vacuum conveying lines, ensuring powders can be check-screened in one dust-tight operation. The sieving unit is also quick and easy to dismantle, reducing downtime between processes. As well as DownFlow Booths, Howorth engineers high containment isolators to provide fully-contained environments for API handling. These isolator systems combine containment to nanogram levels with integrated equipment to provide maximum production, ergonomic and maintenance
CASE STUDY: PURIFICATION & FILTRATION
efficiency. For the containment isolator process, APIs would be loaded into the isolator using a drum-loading chamber with the product vacuumconveyed and sieved, then deposited into the same IBC as described previously. For this particular customer, a hybrid sieving system was engineered, combining a Russell Compact Airswept Sieve with the Russell Compact Airlock Sieve clamping system. THE BENEFITS The custom-built containment powder screener provided all the benefits of vacuumconveying sieve technology with the patented TLI (twist, lock and inﬂate) airlock clamping system — designed to provide effortless operation, ideal for pharmaceutical sieving in a glove box. An additional inlet was also incorporated to allow for manual scoop-feeding of powders on a smaller scale. To further improve usability, Howorth’s glove boxes have an integrated clean-in-place system
with hygienic spray balls and a wash hose to allow easy washdown of equipment after use. The user-friendly Russell Compact Airlock Sieve TLI (twist, lock and inﬂate) clamping system provides effortless operation whilst maximising screening performance. The system is easy to use, and requires significantly less space than alternative clamping methods. Simply place the component parts into the base and locate them by twisting and locking the lid. An inﬂatable seal then locks the components in place. This reduces the dust and improves operators’ health and safety, providing OEL 5 containment (less than 1 µg/ m3). The system also means these units are quick and easy to dismantle in areas of limited space, such as containment isolators. “We chose to work with Russell Finex on this project because of the wide range of compact pharmaceutical screening equipment available, including the Russell Compact
Airlock Sieve which provides a significant ergonomic advantage when operated and maintained within the constraints of a containment isolator,” continued Stanway. “Support provided by Russell Finex during the design and mock-up phase was also invaluable. When providing premium custom-built solutions such as this, it is imperative the equipment we integrate is of a high quality, operator-friendly and versatile to meet specific functions and environments.” With a range of sizes and configurations available, this range of pneumatic pharmaceutical sieving equipment is suited to integration inside areas of limited room such as pharmaceutical downﬂow containment booths and containment isolators. Included in this range is the Russell Compact Airswept Sieve, which features dusttight operation reducing the risk of product inhalation, and an easy-clean and strip down design to minimise production downtime.
with validated fluid path solutions
Our puresuÂŽ single-use assemblies combine our tubing, hose, connectors, gaskets and clamps into custom end-to-end fluid paths that are traceable and dependable. puresu is pre-validated to simplify your compliance with the latest industry regulations and GMP requirements. Whether in single-use or stainless process, our range of Watson-Marlow peristaltic pumps, ASEPCO valves, BioPure single-use fluid path components, Aflex PTFE hoses, and Flexicon aseptic fill/finish systems all work together to deliver batch to batch consistency and repeatability throughout your product development.
Visit us at Hall 3.1, Stand E70
Whatever the weather We speak with Chapper healthcare’s warehouse manager, Stephen Prior, about overcoming the logistical challenges of shipping medicines around the globe and the packaging solutions his team utilise to overcome every eventuality, including the weather.
Q. CAN YOU EXPLAIN MORE ABOUT YOUR ROLE AND WHAT IT CONSISTS OF? A. I am in charge of the overall running of the warehouse and manage the logistics for temperature-controlled shipments of speciality pharmaceuticals. This includes sourcing the right packaging, validated cool boxes and temperature loggers for all our shipments. The types of medicines we ship around the world range from ambient products to highly specialised temperature-controlled pharmaceuticals that require very specific packing. Each product and its onward journey to the customer will have its own unique set of challenges. As an example, we regularly export products that require different temperature ranges such as 15–25°C, 2–8°C and frozen products. Therefore, it is important to understand shipping processes, temperature control, customs regulations and the sensitivities around getting products to patients on time so they can be treated. Q. CAN YOU EXPLAIN MORE ABOUT HOW MEDICINES ARE SHIPPED AROUND THE WORLD TO CUSTOMERS AND SUPPLIERS? A. One vitally important element of the process is the correct
packaging of the products. Using the right type of packaging will avoid breakages and make sure that the product is suitably protected throughout its journey, whether this is by air, sea or road. To prevent breakages, special boxes, which are extremely strong and durable, can be used. Additionally, it is important to do everything possible to maintain the integrity of products so that nothing is broken in transit. For example, liquids can be placed in plastic bags, to prevent contamination of other products (in the unlikely event of a breakage), packs of vials can be bubble wrapped and for bottles corrugated tubes can be employed for protection. It is crucial that every product reaches the customer in pristine condition. Temperature-controlled shipments can be packed in validated boxes — for these, we perform our own internal testing, in addition to reviewing the manufacturers test data to ensure that the boxes will maintain the correct product temperature throughout the duration of the journey. Clear labelling, with warning labels, ensures anyone handling the boxes is made fully aware of the delicate contents. Another technology for use in temperature-controlled shipments is a USB temperature logger. This technology can be used by the shipper and client to review the temperature throughout the duration of the journey to
ensure there have been no temperature excursions. Q. WHAT OTHER SPECIAL FEATURES CAN PACKAGING HAVE? A. Temperature-controlled boxes can be designed to keep their temperature for a set amount of time depending on where in the world the package is travelling to. For example, if a product is going to Europe a box which lasts for 48 hours would be suitable and if the product is going further then a box which lasts up to 120 hours would be better to ensure the temperature is controlled for the duration of the journey. Additionally, it is important to factor in ﬂight delays and that products need to be cleared through customs which can all add to the length of the journey. Q. WHAT ARE SOME OF THE CHALLENGES OF SHIPPING PRODUCTS AROUND THE WORLD? A. The cold weather across most of Europe this winter has been particularly challenging. Temperatures were below freezing for a number of weeks, which made it difficult to ship products correctly and ensure they didn’t freeze. Pharma products have temperature stability data and the products are only viable if they are stored within
a particular temperature range. To adhere to this, we adopted the latest advances in temperaturecontrolled boxes: Some of the boxes we use are made of Phase Change Material (PCM) — meaning they can be placed in a fridge once packaged up, which is unusual as most other boxes can’t. This type of specialist packaging means the products are kept in the correct temperature range in a fridge or if the weather is particularly cold outside. The PCM packs go into hibernation mode if it is below a certain temperature outside which ensures the products are kept at a constant temperature in the box and temperatures do not deviate above or below the allowed range. Furthermore, these PCM boxes are reusable and we encourage clients to send them back to us, so we can repack the boxes for them, this is also important to us from an environmental perspective.
Q. WHAT OTHER LOGISTICAL CHALLENGES CAN BE FACED IN SHIPPING?
Q. WHAT ABOUT SHIPPING PRODUCTS TO HOT COUNTRIES, DOES THIS IMPACT THE TYPE OF PACKAGING?
Q. HOW IMPORTANT IS CUSTOMER SERVICE?
A. It is equally important to ensure the temperature is controlled for sensitive products when shipping to a hot country as it is for a cold country. For extremely hot climates, such as the Middle East in summer, special boxes, which may have a lifetime of up to 144 hours, can be used to ensure products stay within the required temperature range.
A. It is vital to ensure that all products leaving the warehouse have the correct paperwork, to prevent any delays in transit. For example, controlled drugs will require import and export licences. It is also worthwhile spending the time developing relationships with reputable freight forwarders and couriers. The people we work with, for example, are experts in dealing with pharmaceuticals and temperature-controlled shipments and they ensure that our customer services levels are maintained until the package reaches its destination. Through our knowledge and that of our logistics partners, we have learnt to anticipate any problems that can arise due to the specific documentation requirements of particular customs authorities.
A. Whether it’s a small one-off shipment or the delivery of several containers, exceptional customer service and supplying products safely, securely and on time is a must. As a team we are fully aware that there is always a patient at the centre of every request.
Whether it’s a small one-oﬀ shipment or the delivery of several containers, exceptional customer service and supplying products safely, securely and on time is a must.
Getting the price right With the global pharmaceutical packaging market growing, partially as a result of improvement in the emerging market, there is a potential for supply chain costs to rise. However, approached in the right way, it will be possible to allow medicines to remain aﬀordable for people living in developing economies while also ensuring they arrive in good condition. Here, Paul Terry, director of sales EMEA at Peli BioThermal, goes into more detail…
he global pharmaceutical packaging market is anticipated to reach an estimated value of $86.4 billion by 2023, according to the latest figures from ResearchAndMarkets.com.1 Further, the annual compound growth rate is expected to be around 5.5% over the next five years.1 This upturn can be attributed to the overall growth of the pharmaceutical industry as well as improvements in healthcare services in emerging markets. Additionally, I believe that the emerging markets approach to standards and applying regulations already in force across Europe (GDP guidelines for example), will definitely be a development area for pharmaceutical packaging over the coming years.
More recently, we have seen growth in the requirement of temperaturecontrolled supply solutions, some of which is driven through the development of more complex and more sensitive compounds and biologics. But the tighter regulatory oversight of the thermal stability in the supply chain has also been a factor in that growth. Therefore, achieving a suitable thermal performance at a cost that is justifiable to the clients and ultimately to the end user is a primary goal. As we’ve developed our products, for example, we’ve focused on the qualified performance levels (high, medium, low) required by the customers so that it is possible to deploy the appropriate level of protection at the right cost for the customer.
Ultimately, this could drive up the costs of supply chains but done in the right way would still allow medicines to be affordable for many people living in developing economies and crucially arrive at the patient in good condition to be part of an effective treatment programme.
Through our design, we have been able to work on achieving a low total cost of ownership by focusing on payload efficiencies and easeof-use of our solutions. Another way that we have managed to reduce the cost to the client is by deploying reusable systems.
CHALLENGES OF TEMPERATURE CONTROL Since our beginnings, we’ve worked extensively with many pharmaceutical companies and their logistics providers. Initially, developing bespoke, tailored solutions, these have evolved over the years into a range that meet many of the challenges facing the temperature-controlled supply chain.
REUSABLE SYSTEMS Reusable systems can not only reduce the associated handling costs when dealing with protective systems in the supply chain but also have the bonus of being more environmentally-friendly.
Controlling temperature conditions is vital to maintain pharmaceutical product stability and effectiveness.
Our range of reuse systems, called Crēdo shippers, are available in a full range of size solutions — from 2L to full pallet. By using a reuse system, customers are able to reduce waste created from packaging and can offer a space
efficient solution, which reduces the vehicle and air cargo hold space and ultimately the energy consumed in the supply chain. However, these reuse systems may not always be suitable. In these instances, we have developed single-use solutions (Chronos and CoolPall shippers) that do not use composites or glues so that they can be easily stripped down into the component parts making recycling at the destination possible. Although, I would say over half the shipments made with our products are now shipped with reusable systems. WHAT DOES THE FUTURE HOLD? As logistics providers improve their return capability and packaging suppliers, like us, continue the establishment of global refurbishment and preparation centres, reusable solutions will continue to thrive. Outsourcing the management of the packaging allowing a ‘load and go’ service for the pharma companies is a likely destination over the next five years. As for the packaging design, I can see a continued development of effective thermal performance with a higher payload efficiency and reduced material costs as more materials are developed and researched. This leads to better thermal performance, more payload efficiency and reduced costs of thermal protective packaging. REFERENCE:
1 | https://www.researchandmarkets.com/ research/l4r96r/global?w=4
33rd International Exhibition for Fine and Speciality Chemicals NEW:
gramm Partnering Pro
The industry’s premier sourcing and networking event Some 400 international exhibitors offer bespoke solutions and specific substances to enhance products or develop new chemical solutions.
s Top conference s p and worksho insights offer valuable &D projects! into ongoing R
Lecture Theatre Agrochemical eers Clinic Chemspec Car e Theatre ur ct Pharma Le cture Theatre Le es ic Regulatory Serv eatre RSC Lecture Th ups tar St e tiv va Inno
Fine and speciality chemicals for various industries: • pharmaceuticals • agrochemicals • petrochemicals • cosmetics • adhesives & sealants • paints & coatings • polymers • biotechnology • colourants & dyestuffs • food & drink • industrial cleaning • reprography & printing • water treatment and much more.
Koelnmesse Cologne, Germany
20 – 21 JUNE 2018 www.chemspeceurope.com
20 – 21 June 2018 | Koelnmesse Cologne, Germany
LOGISTICS & DISTRIBUTION
Come fly with me… Here, we speak with Sergey Lazarev, general director of AirBridgeCargo Airlines about logistics in the pharma market, what it means to be an IATA CEIV Pharma-certiﬁed company and the future of pharma transportation. Q. COULD YOU GIVE A BRIEF OVERVIEW OF AIRBRIDGECARGO (ABC) IN GENERAL AND WHAT MAKES YOU UNIQUE IN YOUR SERVICE TO THE PHARMACEUTICAL INDUSTRY? A. ABC is a global cargo airline that is expanding its route network to connect customers in the transregional markets of Asia, Europe and North America, covering more than 30 major cargo gateways and accommodating trade ﬂows worldwide. All the ﬂights are operated via ABC’s cargo hub in Moscow Sheremetyevo airport, enabling connection throughout the airline’s expanded international network within a 48-hour delivery time, including handling. There are hardly unique air carriers for transportation of pharmaceuticals, as each carrier tries to handle this special cargo in the most effective manner. AirBridgeCargo has been developing its abc pharma product with an understanding of how it might benefit the end consumer (patient). On top of this, we always partner with supply chain stakeholders that share our corporate values and understand that development of this sector is possible through joint efforts, cooperation and data-sharing. Q. WHAT SHOULD SHIPPERS LOOK FOR IN A SPECIALIST PHARMA PRODUCT? A. Shippers look at service quality, proven track record of successful pharma operations, IATA CEIV certification (which serves as an industry benchmark), diversified ULDs and pharma containers, extensive international network with QEP accreditation, certified and skilled personnel, availability of online information, as well as the possibility to have a one-call
option to figure out all the shipment records and status. Q. WHAT DOES IT MEAN TO BE AN IATA CEIV PHARMACERTIFIED COMPANY? A. With an increasing number of regulations around the world to implement and comply with it has become evident that the supply chain industry needed unified, globally consistent and acknowledged regulations or certification to serve as a benchmark for the market, and customers. IATA CEIV has become just this. To sum up, the benefits ABC has gained so far through IATA CEIV certification: ● Certified and trained personnel to handle temperature-sensitive products ● Certified facilities, equipment, premises and aligned handling procedures ● Implementation of best practices ● Acknowledgement and compliance of all internal process with high requirements of pharmaceutical industry ● Reduced number of audits required ● Possibility to speak ‘one language’ with the industry ● Cooperation with companies, partners, sharing the same values in transportation of pharma products Q. RECENTLY, ABC AND SHANGHAI PUDONG INTERNATIONAL AIRPORT CARGO TERMINAL (PACTL) SIGNED MEMORANDUM OF UNDERSTANDING (MOU), COULD YOU GIVE US MORE DETAILS ON THIS NEW AGREEMENT? A. The Pharmaceutical sector sets a high level of expectations for all supply chain stakeholders.
Understanding the need for highend services our customers expect us to provide, we have entered into collaborative relationships with partners, such as PACTL. Through our latest MoU with PACTL, we will look to promote the time and temperature sensitive products transportation and deliver the best service to our customers. We believe that our joint efforts in this regard could make a significant contribution to the development of the pharma market for both companies. Q. DO YOU EXPECT PHARMA VOLUMES TO CONTINUE TO GROW AND WHAT ARE YOUR CUSTOMERS’ REQUIREMENTS? A. Transportation of pharmaceuticals is a big business, complex, demanding, requiring a high level of standards’ compliance. But most importantly, is that a human life can depend on the actions and operations taken during the transportation process. The driving growth in handling pharma products is the desire of the end consumer to have the latest medicine available, when and where needed, or for doctors to have essential medical supplies. Development of the latest vaccines, medicines, vitamins to protect health also stimulates a boom for transportation of pharma products. The pharma sector shows significant growth rates around the world, with logistics being no exception. Customers’ requirements are very simple — reliable and safe transportation, with available realtime, round-the-clock tracing info, which should be easily readable and understandable.
WEâ€™VE DROPPED A SIZE AND GOT A NEW LOOK As the authoritative voice in its sector, European Pharmaceutical Manufacturer is updating its look to showcase its pertinent, targeted and BPA-audited content. Covering the entire pharma and biopharma manufacturing supply chain from clinical trial to mass production, regulations, and logistics and distribution, European Pharmaceutical Manufacturer expands readersâ€™ knowledge of new technologies and innovation that helps bring drugs and medicine to market.
For advertising opportunities contact: ROB ANDERTON
+44 (0) 1244 952 359 email@example.com
+44 (0) 1244 952 519 firstname.lastname@example.org
Navigating the mHealth maze This latest instalment of Tech Talk looks at development considerations for mHealth apps, Dr Neil Polwart, Novarum founder and BBI Group head of mobile, tells us more…
obile is touching all our lives and it’s almost inevitable that at some stage your organisation will consider developing a mobile application to tap into this emerging market. Designing successful mobile applications is far more than just engaging with a graphic designer to develop attractive screens or reworking web content so it’s optimised for mobile. Before the design journey, you must be sure you are solving a real problem or adding value for the user (not just your organisation). It may be that you need to tailor parts of your app to suit different users. A pharmacist, doctor or patient all have different information needs and likely regulatory considerations. You also need to consider where they will use it and understand if mobile is the right solution. One key consideration is the availability of a reliable network connection. If a good connection is available and no sophisticated hardware functionality is required,
it may be possible to provide the capability in a mobilefriendly website without requiring the user to download and install an app. If wifi or good cellular connections are not available all the time, then it will be inevitable that the functionality is provided in an app. The landscape for developing mobile apps is constantly changing, but since Microsoft moved away from the mobile arena, this has simplified the problem. Even then, you have thousands of different device capabilities with dozens of different screen sizes to accommodate. A good app developer will be able to guide you through the maze of options available, including the pros and cons of true native app development (completely separate apps for Android and iOS) versus hybrid apps based on web-technology. To maximise the userexperience from a mobile app, and differentiate it from other digital tools, you should consider how to benefit from mobile phone features and
accessories, such as the camera, motion sensors and GPS, for example. As well as integrating with hardware on the user’s device you can look to become more closely linked to the ecosystem on their phone by interfacing with their calendar app, linking to contacts, or populating data into health tracking apps. Whichever app you interface with, communicate it to the user clearly. Depending on the app and the type of user you are dealing with it might be appropriate to interface with their social media accounts. Obviously for many medical, clinical or pharmaceutical applications this sort of use will cause significant privacy concerns. However, in some instances, sharing carefully selected useful information will help extend the reach of your app. Positive user-experiences encourage users to return to the app and help make it ‘sticky’ — recurring regular users who value it.
Push notifications are another example where mobile opens up options for better interaction with users. Careful and considerate use of these notifications can help keep users engaged, or bring users back to an app they neglected. Ultimately, most mobile apps are trying to get users to perform some sort of transaction, whether that is making a purchase, recording data or accessing information in a convenient form. It can be hugely helpful for businesses to understand where, and possibly even who, is accessing information. It may guide future product development, so tracking analytics on app usage and transactions is important. Achieving loyal users who repeatedly use ‘sticky apps’ is all about the quality of the experience they receive. Each use case is different, in some cases stability and familiarity is important. In others, a constant stream of new features or content helps keep users engaged.
11 – 15 June Frankfurt / Main
BE INFORMED. BE INSPIRED. BE THERE. › World Forum and Leading Show for the Process Industries › 3,800 Exhibitors from 50 Countries › 170,000 Attendees from 100 Countries
The June 2018 issue of EPM Magazine is available for download with all the regulars and features on biologics, solid dosage solutions, Queen...
Published on Jun 11, 2018
The June 2018 issue of EPM Magazine is available for download with all the regulars and features on biologics, solid dosage solutions, Queen...