ISSUE 33 • JUNE 2017www.industrialpharmacy.eu

www.eipg.eu

Why pharmacistsshould studycompaction:

Part 2 – making better tablets

Raising awareness ofthe dangers of fake

medicines

Cyberattacks on thepharma industry

Why pharmacistsshould studycompaction:

Part 2 – making better tablets

Raising awareness ofthe dangers of fake

medicines

Cyberattacks on thepharma industry

europeanINDUSTRIALPHARMACY

2 european INDUSTRIAL PHARMACY June 2017 • Issue 33

europeanINDUSTRIALPHARMACY

June 2017ISSN 1759-202X

MANAGING EDITORPhoebe SpeisPRODUCTIONSue Feather

SUBSCRIPTIONSJill Monk

EDITORIAL BOARDMichael AnisfeldClaude FarrugiaMichael GamlenChing-Yi HsuJohn Jolley

Giorgos Panoutsopoulos

European Industrial Pharmacyis published four times a year by: Euromed CommunicationsPassfield Business Centre,

Lynchborough Road, Passfield,Liphook, Hampshire GU30 7SB

Tel: +44 (0)1428 752222Fax: +44 (0)1428 752223

Email:info@euromedcommunications.com

www.eipg.eu/eipg-journal

Indexed by:Scopus & Embase

Views expressed in European IndustrialPharmacy are those of the contributorsand not necessarily endorsed by the

Publisher, Editor, Editorial Board, or by ourcorporate sponsors who accept no liabilityfor the consequences of any inaccurate or

misleading information©2017 Euromed Communications

europeanINDUSTRIALPHARMACYdiscussion group:

www.pharmweb.net/gmp.html

european INDUSTRIAL PHARMACYis the official publication of the European IndustrialPharmacists Group (Groupement des Pharmaciens del’Industrie en Europe) www.eipg.eu

features4 WHY PHARMACISTS SHOULD STUDY COMPACTION:

PART 2 – MAKING BETTER TABLETSImproving tablet quality using a new lab test methodologyby Michael Gamlen

7 RAISING AWARENESS OF THE DANGERS OF FAKEMEDICINES: THE MAKING OF A WORLD HEALTHPROFESSIONS ALLIANCE VIDEOIn 2016, the World Health Professions Alliance, as part of itslong-term work against fake medicines, released a campaignvideo “Counter the Counterfeits”. This article shares how thisproject — led by the International Pharmaceutical Federation— came to fruition.by Lin-Nam Wang

11 CYBERATTACKS ON THE PHARMA INDUSTRYCyberattacks in the pharmaceutical industry – why are theyso easy and how can they be prevented?by Dr Nicola Davies

regulars3 EDITORIAL COMMENT

15 REGULATORY REVIEW

23 PHARMA IN PLENARY

25 BOTTLED BROWN

26 EIPG NEWS

29 EUROPEAN MEDICINES VERIFICATION ORGANISATION(EMVO) PROGRESS MONITORING REPORT

30 EVENTS

The European Industrial Pharmacists Group extends a special thanks to Walgreens Boots Alliance and AesicaPharmaceuticals for their kind support of the publication of this journal.

Newton’s laws,Einstein’s theory orjust plain science?Time is running out fast. Itmay not seem that way – afterall, we started with just over1000 days between thepublication of the DelegatedRegulation governing thedetails of the safety features,and there are still about 600days to go. However, adviceissued by both the EuropeanMedicines VerificationOrganisation (EMVO) and theblueprint providers indicatethat in any national system atleast 6 months of testing withall users connected to thesystem are recommended,which means that for anycountry behind schedule, there areapproximately 400 days – just over a year – leftto get all systems on line for a testing phase.Once again, the progress report issued by

EMVO makes for sombre reading – only sevencountries have signed a contract with the serviceprovider and almost two-thirds of countries arebehind schedule – which means that theblueprint providers will be faced with a numberof national systems requiring commissioning,and the hub of the same systems coming on lineen masse, close to the deadline, instead of in anideally gradual manner. The irony – if notoutright concern – is that the countries that areahead of schedule or mainstream, for the mostpart, are countries with lower percentage lossesin sales due to intellectual propertyinfringement, according to the figures of the EUIntellectual Property Office, whilst at least half ofthe cohort of countries who are behind schedulerank in the top third of countries suffering fromthese losses, and which, therefore, seem to bemost at risk – at least in relative terms in theEuropean territory – of the presence ofcounterfeit medicines products in theirpharmaceutical supply chain. Clearly, an impetus is needed – if nothing else

to address lacunae inknowledge about how theentire system will operateonce it is fully operational. Itwould probably be amiss tobelieve that, in Newtonianfashion, greater efforts willlead to a proportionatelygreater speed towards theobjective. There are so manyconsequences arising fromthe regulation, many relatedto professional practice aswell as technicalimplementation, thatprogress appears to beEinsteinian in nature – theprogressive increase in thesize of the challenge makesevery extra amount of energyput into achieving the

objective appear less effective at actuallymoving faster towards the goal. Yet, just as scientists continue to pour their

efforts into overcoming the limitations ofEinstein’s theory, so must the world of pharmacontinue to reach for the ultimate aim ofprotecting all patients from counterfeitmedicines. Relative amounts of counterfeitmedicines in the EU compared to extra-European markets are of little comfort as long asthe patient in every box is at risk. Moreover, justas scientists believe that the universal nature oftheir work is the key to their eventual success, somust the world of pharma remove all barriers tothe universal participation of any pharmaceuticalassociation – trade or professional – in thisproject. It is only through the active participationof all such associations that the project can hopeto achieve the level of success that theinvestment of finance, time and effort demands.

Professor Claude FarrugiaPresident, EIPG

3

editorial

european INDUSTRIAL PHARMACY June 2017 • Issue 33

european INDUSTRIAL PHARMACY June 2017 • Issue 334

Improving tablet quality byunderstanding the compactionprocess is becoming a reality. Irecently visited India to demonstratefor our compaction analysis systemto possible purchasers. The systemincludes two pieces of kit, thecompaction analyser and the tensiletester, which travel in flight caseswell within the airlines weight limits.I was travelling with our agent whohad an extensive tour planned for us– three cities in 3 days, five clientvisits in all. In addition to the keyinstruments, I also carried a powderpipette – a small dispensinginstrument which dispenses a fixedvolume of powder and removes theneed for sample weighing duringthe demonstrations. Travel in India isalways interesting (challenging!)especially at busy domestic airports.Security were not often interested inthe instrument itself but found thepowder pipette, which is vaguelygun-shaped, a great challenge.Our agent GS had visited us in

London prior to the visit to get moreinformation on the system, which setme the challenge of how to quicklydemonstrate to him the impact ofmaterial properties on compactionbehaviour. He has a technical

background but no directexperience of tableting. In the past,we have used a small roller system,marketed for grinding small stones,as a roller mixer to demonstrate theimpact of material properties onmixing behaviour. I decided that wewould use this to demonstrate theimpact of lubrication on tabletproperties, using two lubricants andtwo blending times. Usingmagnesium stearate as a “control”(?worst case material), and sodiumstearyl fumarate – my preferredlubricant, I planned to do a simplecomparison of 5 and 10 minutesblend on the compaction propertiesof a direct compression excipient.Audience participation is a great

way to get people interested, sowhile I used the powder pipette todispense fixed amounts of powder(about 70 mg for a 5 mm tablet) andmake the tablets, GS measured thetablet fracture stress and chartedthe values. As we were doing asimple comparison, we did notmeasure tablet thickness or weight;the pipette keeps the weight fixedand the thickness did not vary agreat deal in the compactionpressure range of 80–180 MPa (200–500kg) which we were studying. We

collected compaction and breakingstrength data on the four samples inless than an hour, and were able tosee that whereas magnesiumstearate reduced tablet strengthafter 10 minutes blending, sodiumstearyl fumarate showed no effect ofblending time – and made bettertablets. When we arrived for our first

presentation in India, it was clearthat the time available was notgoing to permit even a shortevaluation of processing. The clienthad two samples from productbatches made from two differentbatch sizes and which had givendifferent results. They wanted toknow if we could see the cause ofthe difference in behaviour. Again,we used the audience to assist withdata measurement and recording.We prepared just one tablet at eachof five forces from the two samplesand got virtually identical results.This is not what the client wanted tohear! But actually, knowing that theprocess has produced the samematerial on two different scales wasan important result. It showed thatthe observed differences resultedfrom the operating conditions of thetableting system and not the blendmanufacturing process. It alsoshowed that the compressibility ofthe formulations was marginal, andthat increasing the compaction forcedid not result in increased tabletbreaking strength. This is the suresign of a risky formulation as theoperator is likely to increase thecompaction force to get a “better”tablet and instead cause capping –as happened here. Another client visit stretched my

data handling skills, to produce aneasier way to visualise ourcompaction data. Our systemuniquely measures both thecompressibility and the lubricity of aproduct. We assess thecompressibility through themeasurements listed in Part 1 of thisseries1 – plots of tabletability,compressibility and compactibility.The target value for tabletability(compaction pressure versus tablettensile fracture stress) is a strength of2 MPa at a pressure of 200 MPa. Thishas been accepted by most of thepharma majors as a desirable value,

WHY PHARMACISTSSHOULD STUDYCOMPACTION: PART 2 –MAKING BETTER TABLETSby Michael Gamlen

Helping people make better tablets is an interestingchallenge – and the challenges are not only

scientific! In this article, a new approach to tabletcharacterisation is described which has been shown toreduce development times and improve product quality.Using the latest technology, it is possible to check thecompaction and lubrication properties of tabletformulation during routine quality control testing.

Michael Gamlen studied for a PhD with Professor JM Newton at Nottingham Universityand was Head of Solid Dosage Form Development at the Wellcome Foundation Ltd for15 years. He is the inventor of the Gamlen Powder Compaction Analysis System, andworks as a consultant and trainer. He is a regular contributor of articles on tableting andpowder compaction.

5european INDUSTRIAL PHARMACY June 2017 • Issue 33

WHY PHARMACISTS SHOULD STUDY COMPACTION: PART 2 continued

with a lower fracture stress limit ofaround 1 MPa at the same pressure.The relative density of the product istargeted at 90% or less, althoughactually values up to 95% are notuncommon. The risk of high densityformulations is over-compaction andcapping. Lubricity is assessed bycalculation of ejection anddetachment stresses. Ejection stressshould not exceed 5 MPa. There isno agreed standard for detachment(take-off) stress but we recommend asimilar limit as for ejection. I was very pleased to discover that

it is possible to generate gradientbackgrounds in Excel charts whichcan be two (or more) colours, andturned at an angle while goingthrough the origin. The results canbe seen in Figures 1–3. Plot lineswhich lie in the green zone areacceptable whereas plot lines in thepink/red zone are high risk. As youmight expect, there is significantblurring between the boundaries asthese factors are not clear cut.We decided to use this approach

in the evaluation of directcompression product targeting the

orally dispersed tablets market. Awell-validated approach toevaluation of direct compressionmaterials, developed by my friendsColin Minchom and Tony Armstrong,is to measure the effect of addingprogressively more of a test materialto the direct compression systemand measuring the effect ontabletability (see above). Using our powder compaction

system, we were able to check thecompaction and lubricity profiles offour levels (5, 10, 20 and 40%) ofpoorly compressible material(ascorbic acid) modelling a drugsubstance. As expected, theexcipient system itself was highlycompressible, and well lubricated(with sodium stearyl fumarate!). Thetablet tensile fracture stress at 200MPa was around 6 MPa – sotabletability was well in excess ofthat needed for a good product. Weestimated the density of the productat around 90%, well within safebounds, and the ejection anddetachment stresses were well below1 MPa – again highly desirable. Aswe added successively largeramounts of model drug, there waslittle effect on tabletability except atthe highest concentration (seeFigure 1) and all the plot lines werewell away from the pink dangerzone. Ejection stress (Figure 2)showed some small increases withincreasing levels of model drug, butremained well out of the 5 MPadanger zone. Detachment stress(Figure 3) showed similar changes tothe ejection stress and again werewell within limits. When wepresented the data to the excipientmanufacturer, they were verypleasantly surprised both with thequality of the data, and the speed ofgeneration. They quickly realised thetechnique’s potential value. Compaction studies based around

tablet fracture are well-establishedhaving been developed in the 1950s.Their major limitation is that for themto work, you need to make, ejectand break a tablet. If you have amaterial which does not make atablet or is not lubricated, then the“make and break” approach cannotbe used. In this situation, what isFigure 2. Excipient mixes Ejection stress.

Figure 1. Excipient mixes Tensile fracture stress (MPa).

6 european INDUSTRIAL PHARMACY June 2017 • Issue 33

WHY PHARMACISTS SHOULD STUDY COMPACTION: PART 2 continued

needed is a system to evaluate thecompaction process itself during thecompaction event. This is known ascompaction analysis – a methodwhich has been widely used withstudies going back to the 1930s. Inmy next article, I will discuss theutility and limitations of compactionanalysis, the pitfalls and theproblems, and how we mightovercome them in the future.

References1 Gamlen M. Why pharmacists should study

compaction: part 1 – introduction. europeanIndustrial Pharmacy 2017;32:4–6.

2 Minchom CM and Armstrong NA. Aproposed technique for expressing thecapacity of direct compressible tabletdiluents. In: British PharmaceuticalConference Science Proceedings, 124thMeeting, Manchester, UK; 14–17September 1987. J Pharm Pharmacol1987;39 Suppl:69–72.Figure 3. Excipient mixes Detachment stress.

7european INDUSTRIAL PHARMACY June 2017 • Issue 33

Disability and deathInterpol estimates that a millionpeople are killed by fake medicineseach year2. Of these deaths, around12% are caused by people takingfake antimalarials in Africa, wherealmost a third of these products arecounterfeit3. Citizens of developedcountries have also been affected,with casualties including 149 killedby fake heparin in 2007/08 in theUSA, for example4. Permanentdisability, prolonged illness, spreadof disease and resistance totreatment add to the harm thatcounterfeit medicines inflict on oursocieties. What is particularlyrepugnant about this criminal activityis that people are being hurt bysomething they take in the beliefthat it will help them. Moreover, it isthe most vulnerable in our societies— the sick and the poor — who tendto be most at risk. Despite the police raids that seize

millions of dollars’ worth of thesepotentially deadly products andmoves to roll out anticounterfeitingmeasures, such as track and trace,the problem of fake medicinesappears to be growing. The internethas made it all too easy for fake andsubstandard medicines to reachconsumers. In some countries, fakemedicines continue to be sold byhawkers in markets, at road sidesand even on buses. That somemedicines are prohibitivelyexpensive and, in some cases, aconsumer preference for anonymouspurchases only serves to exacerbatethe situation.

Deep concernIt should come as no surprise thathealthcare professionals are deeplyconcerned about fake medicines.For a number of years, the WHPA,which gathers together globalfederations of pharmacists, nurses,

doctors, dentists and physicaltherapists, has been advocating formore action as part of its mission toimprove global health and patientsafety. Surveys in Europe, Asia and the

USA indicate that the general publichave low awareness of the existenceof fake medicines and theirassociated risks5–7. It is clear thatimproved education and awarenessare part of the solution. The WHPA’s work has included

making grants to countries to runnational counterfeit medicinesawareness projects and producing ahandbook for health professionalsentitled “All you need to knowabout spurious medicines”8. Mostrecently, however, it resolved tobroaden the scope of its campaign,aiming to gain a more internationalreach, and deliver messages to threetarget audiences: the public, healthprofessionals and policymakers. Buthow?

A new projectIt was clear that making a videocould be an answer. Video hasbecome a key communications toolin education and marketing, allowinginformation to be spread throughoutthe world in a matter of seconds andto any number of devices. Peopleare watching more and reading less.Moreover, humans are audio-visualcreatures and video, by engagingthe senses of sound and sight,makes more of an impact. But theestablished popularity of video as acommunications channel also meantthat, undoubtedly, there wouldalready be a number of videosraising awareness of the dangers offake medicines. A review of what was available on

the internet confirmed this, showingat least 17 existing videos on thetopic, albeit with mixed results interms of viewing numbers on theircorresponding social media channels— anything from double digits to acouple of hundred thousand.Notably, and as you may expect, thevideos that were the most successfulwere the ones with an element ofshock value or risqué humour. Forexample, a 2009 production by theUK’s Medicines and HealthcareProducts Regulatory Agency and

RAISING AWARENESS OFTHE DANGERS OF FAKEMEDICINES: THE MAKINGOF A WORLD HEALTHPROFESSIONS ALLIANCEVIDEOby Lin-Nam Wang

Ten billion euros is the figure estimated to be lost bypharma each year due to fake medicines, according

to a report from the European Union IntellectualProperty Office (EUIPO) in 20161. This, the EUIPO says,corresponds to 4.4% of the industry’s sales, whichtranslates into direct employment losses of around38,000 jobs. But the cost to health and human life is far,far greater. In 2016, the World Health ProfessionsAlliance (WHPA), as part of its long-term work againstfake medicines, released a video “Counter theCounterfeits”. This article shares how this project — ledby the International Pharmaceutical Federation (FIP) —came to fruition.

Lin-Nam Wang is a pharmacist and communications manager at the InternationalPharmaceutical Federation.

8 european INDUSTRIAL PHARMACY June 2017 • Issue 33

RAISING AWARENESS OF THE DANGERS OF FAKE MEDICINES continued

Pfizer featuring a man regurgitatinga dead rat had over 100,000YouTube views at the end of 2015,and a video from the Federal Unionof German Associations ofPharmacists in 2008, entitled “BigDick sells Viagra” had over 200,000YouTube views. The question was how the WHPA

project could bring something a bitdifferent to the table so as to ensurethe best use of a relatively smallbudget. A brainstorming session ledto the idea of exploiting a functionof YouTube to incorporateinteractivity into the video. Wewanted to confront the viewer with asituation to which relatively littlethought is often given — buying amedicine — and to send home themessage that there is a need to thinktwice about the choices he or shemakes. At this stage, we decidedthat we wanted a split screen videoshowing two scenarios and askingthe viewer to choose between twoproducts (see Figure 1).

Preparation and action One of the most vital stages in theproject was to write a good brief,incorporating the key messages wewanted to give to each target groupand communicating that fakemedicines pose a universal threat topeople in all countries and of allages. It was important to clarify ouraims. We wanted to warn people, ingeneral, of the risks of fakemedicines and help them to avoidthe harms that they could cause. Atthe same time, we wanted toprovide guidance to healthprofessionals on how to avoidbecoming inadvertent suppliers offake medicines and what to do if apatient suspects that he or she hastaken a fake. We also wanted to callon policymakers to take greateraction on this issue. A fundamental step was to draft a

script that included all thesemessages, approved by each of theWHPA partners (see Figure 2). This,along with the brief, was given to thevideo production companiestendering for the project, for theirinput. From the tenders and

proposals received within thebudget, it was decided that, since all

three target groups were, essentially,consumers, a single video would be

Figure 1. Asking the viewer to choose between two products.

Figure 2. Storyboard sketch of the video content.

9european INDUSTRIAL PHARMACY June 2017 • Issue 33

RAISING AWARENESS OF THE DANGERS OF FAKE MEDICINES continued

produced, accompanied by threefurther, more targeted parts. Tone and style were a careful

consideration. We thought that tobetter communicate that the risks offake medicines are real, actors ratherthan animated characters, forinstance, should be used for the firstvideo despite the higher associatedproduction costs. The three furtherparts, containing guidance for eachtarget group broken down into fiveor six avoidance “measures”, wereanimated (see Figure 3). Table 1shows the measures for consumersand Table 2 shows the measures forhealthcare professionals. Wanting an international reach

also brought up a question oflanguages in addition to English.French, Spanish and Arabic wereconsidered as priority languages fortranslation, which could be providedwith little cost through the WHPAnetwork.It was also important, at an early

stage, to have a communicationsplan in place for disseminating thevideo as widely as possible once itwas made. Potential distributionchannels were listed and includedthe WHPA and its partners’ websites,publications, social media accountsand press contacts, national memberorganisations of the WHPA partners,other campaigners against fakemedicines and governments. The filming of the video took 2

days and, because of a relativelysmall budget for what we wanted toachieve, it was an all-hands-on-deck

exercise. FIP and productioncompany staff and friendsvolunteered to take part so as tofeature people of as many races andages as possible throughout each ofthe 24 scenes. Accuracy, authenticityand the need to avoid identifiablebrands were also high on the list ofpriorities. Mock but realistic packs ofmedicines were produced as props,as well as a mock-up onlinemedicines retail website. We alsomade full use of our pharmacycontacts to provide generic lookingtablets and to allow filming to takeplace in a hospital. Figure 3. Animated guidance measures within the video.

Tell your healthcare professional if a medicine has no effect or an unexpected effect.If you suspect you’ve taken a fake, seek help immediately. But don’t panic and don’tstop all your medicines.

Only buy medicines from authorised sources. Check with your health authority ornational pharmacy organisation whether a supplier is authorised. Never buymedicines at the roadside.

If you buy online, be sure to use an authorised pharmacy. For example, check withyour country’s pharmacy organisation. In the EU, you can look for and click on theEuropean Commission online pharmacies logo.

When you travel, consider taking any medicines you might need with you. Keep inmind that you cannot be sure of safety in unfamiliar circumstances.

Look for anything unusual about the product or its packaging. If you think a medicineis fake, report it to a healthcare professional.

Remain alert to the risks of fake medicines. Share these tips with your family and friends.

Table 1. Measures consumers can take to avoid the harm of fake medicines.

Educate your communities on unsafe sources, what to look for (e.g. intact packaging,properly sealed, clearly labelled with dosing, manufacturer, batch number and expirydate), and what to do if they think a medicine is fake. Lobby your politicians toinvolve them in combating counterfeits.

Keep the legitimate supply chain secure by only sourcing medicine from authorisedsellers. Be suspicious if you are offered a medicine at an unusually low price(especially from a new source).

Inspect your products. Know what to look for. A checklist to help you carry out visualinspections of medicines is available at: www.fip.org/ctc. For example, havetablets/capsules changed in size, shape, colour or odour? Be ready to adopt newpractices and technologies to combat counterfeiting.

When supplying a medicine, tell patients about the expected effects and side effects,including time-span. Tell them to come back to you if the medicine has no effect oran unexpected effect.

If someone thinks they have a fake medicine, act quickly to give health advice,including on emergency care and therapy reassessment. Establish the source ofsupply, if the medicine has been taken and how much, and if there have been anyadverse effects.

If a product is suspected to be fake, warn colleagues and notify the officialmanufacturer. Comply with the instructions of your drug authority (which may includepatient tracing and product recall). Act to avoid disruption of treatment and givebalanced information.

Table 2. Measures healthcare professionals can take to prevent the harm offake medicines.

10 european INDUSTRIAL PHARMACY June 2017 • Issue 33

How did we do?The video and animations, whichwere released in September 2016,can be seen atwww.youtube.com/watch?v=aEJd0T7Nhf4, or scan the QR code below.

The storyline leads to the viewerbeing asked to choose betweentwo products and being shown theconsequence of their decision:depending on his or her choice,either recovery from an illness oradmission to hospital.Since its launch, the video has

had over 168,000 views and reachedover 847,000 people on FIP’s socialmedia alone. Enthusiasm for thevideo was expressed by the WorldHealth Organization andgovernment agencies. The IcelandicMedicines Agency, for example,asked for permission to use it andthe video has been shown on awebsite jointly run by Austria’sMinistry of Health, police andChamber of Pharmacy. A speciallyproduced standalone (non-interactive version) has beenscreened at conferences in China,Taiwan, Ghana, Zambia and Nigeriaand outreach efforts led to mediacoverage in Europe, the Americasand Asia. The “Counter theCounterfeits” standalone video isfree for anyone to use for non-commercial purposes and can beobtained by emailing fip@fip.org.

How else could we stoppeople being killed?FIP views this project as a success. Ifit has prevented even one personfrom harm, then it has been aworthwhile use of resources. But thefight is far from over. Much moreeffort is needed if we are to stopthe tragedy of people being injuredor killed by fake medicines. Wewant policymakers, in particular, todo the following.

• Create strong laws orstrengthen existing policies,such as making reportingmandatory.

• Ensure there are systems inplace for rapid alerts.

• Make sure all stakeholders —police, customs andhealthcare professionals andtheir associations — areinvolved and trained.

• Remain aware of sources ofcounterfeiting in legitimateand illegitimate supply chains.

• Allocate sufficient resources toprotect the public throughstronger enforcement.

• Make sure the health systemhas mechanisms, such asbarcoding or radio-frequencyidentification tagging, in placeto trace legitimate products.

• Seek technologies that helpto protect the supply chain.

• Involve healthcareprofessionals in policydecisions and guidance sothat these are appropriate forreal-life settings and will beput into practice.

• Legislate for strongerpenalties for counterfeiters.

FIP and the WHPA is continuing towork on the worrying issue of fakemedicines, calling attention to theproblem and advocating forsolutions at all levels. Moreinnovative solutions and morecoordinated efforts are needed.

AcknowledgementsFIP is grateful to all those whosupported the production of the“Counter the Counterfeits” video,including St Antonius Hospital inNieuwegein, the Royal DutchPharmacists Association andTransvaal Pharmacy in The Hague;and, in particular, Mr Rob Moss, MrJohan Oltvoort, Ms Judith Bijloosand Mr Paul Lebbink, as well as toall the volunteers who featured in it.We are also thankful for the supportfrom our wide network of national

professional organisations, whichhelped to disseminate the video,and for an educational grant fromLilly, which went towards productioncosts.

References1 European Union Intellectual Property

Office. The economic cost of IPRinfringement in the pharmaceuticalindustry. Alicante, Spain: EUIPO, 2016.Available at:https://euipo.europa.eu/tunnel-web/secure/webdav/guest/document_library/observatory/resources/research-and-studies/ip_infringement/study9/pharmaceutical_sector_en.pdf (Accessed 20 April2017)

2 Southwick N. Counterfeit drugs kill 1mpeople annually. Insight Crime 24 October2013. Available at:http://www.insightcrime.org/news-briefs/counterfeit-drugs-kill-1-million-annually-interpol (Accessed 20 April 2017)

3 Wall M. Counterfeit drugs: people aredying every day. BBC News 27 September2016. Available at:http://www.bbc.com/news/business-37470667 (Accessed 20 April 2017)

4 Bate R. The deadly world of fakemedicine. CNN 17 July 2012. Available at:http://edition.cnn.com/2012/07/17/health/living-well/falsified-medicine-bate/index.html(Accessed 20 April 2017)

5 Sanofi. Press Release: Only 20% ofEuropeans associate counterfeiting withmedicines. Paris, France: Sanofi-AventisGroup, 15 May 2014. Available at:www.fakemedicinesrealdanger.com/web/only-twenty-porcent-of-europeans-associate-couterfeiting-with-medicines(Accessed 20 April 2017)

6 Fight the Fakes. Survey of 5 Asiancountries on awareness of medicines.Geneva, Switzerland: Fight the Fakes, 18December 2015. Available at:http://fightthefakes.org/resources/survey-of-5-asian-countries-shows-higher-awareness-of-counterfeit-medicines/(Accessed 20 April 2017)

7 Fight the Fakes. Survey reveals how littleUS citizens know about fake medicines.Geneva, Switzerland: Fight the Fakes, 27November 2015. Available at:http://fightthefakes.org/resources/study-reveals-how-little-us-citizens-know-on-fake-medicines/ (Accessed 20 April 2017)

8 World Health Professions Alliance. WHPACounterfeit Medical Products Campaign.Ferney Voltaire, France: WHPA. Availableat:www.whpa.org/counterfeit_campaign.htm(Accessed 20 April 2017)

RAISING AWARENESS OF THE DANGERS OF FAKE MEDICINES continued

11european INDUSTRIAL PHARMACY June 2017 • Issue 33

No company, regardless of its typeor size, is invulnerable againstcyberattacks. In 2014, the threeindustries which had the highestthreat for cybercrimes wereaviation, chemical andpharmaceuticals2. In 2015, a studyshowed that more than 66% of thepharmaceutical companiessurveyed had a breach of access,whereas 25% were attacked byhackers3. In the case ofpharmaceutical cyberattacks, theincentives are mainly financial, asthe intellectual property (IP)associated with drug manufacturingare valuable. However, the attackscan also involve corporate spying;pharmaceutical and biotechcompanies contain diverse data,ranging from patient medicalrecords to drug development andclinical trials results, informationwhich is invaluable to competitorcompanies4.

Cyberattacks in pharma:why so easy?Historically, pharmaceuticalcompanies used isolatedinformation technology (IT) systemsthat were not connected to theInternet, hence they were notdesigned for cyber security.However, digital health by means of

health tracking devices, big dataanalytics, remote access, patientdata uploaded to the cloud, sharedaccess with other organisations,and a general connection toexternal environments and theInternet, has led to the Internet ofThings (IoT). E-Health has allowed

pharmaceutical companies to growfaster, to gain access to valuabledata, to develop personaliseddrugs, and better communicateand engage with patients5. Forinstance, Novartis has signed anagreement with technologicalcompany Qualcomm to produce aninhaler which will connect to theCloud and will promote Novartis’new drug for chronic obstructivepulmonary disease, Onbrez. This type of health technology

will allow patients and physicians toaccess patient’s data and medicalhistory at any time and by anydevice. Although this new healthdigitation produces many healthand financial benefits, sensitivepatient information becomesdesirable for striving hackers andcybercriminals6. Through theIndustrial Control SystemsSupervisory Control and DataAcquisition (SCADA) networks,pharmaceutical companies can

connect to all types of externalenvironments and access pertinentdata and analytics. However,SCADA networks wereinadequately designed againstcyber threats7. The lack of securitycontrols became obvious when avery maleficent attack, known asDragonfly or Havex, a virusespecially designed forpharmaceutical companies, allowedhackers to access, impair, and stealdata from pharma IT databases8.Furthermore, the medical device isalso not designed againstcyberattacks. As Mr Valencia,Senior President of Qualcomm Life,states, “They [medical devices]weren't designed with the idea inmind that they would be goingover the network and theinformation would be residing incloud infrastructure.”8In addition, patient data is

scattered across many domains andshared with other organisations,hospitals and academic institutions.Therefore, a breach of access canoccur at any time during the datasharing. Even if one pharmaceuticalcompany has updated cybersecurity systems, there is noreassurance that the otherorganisations maintain the samelevel of security8. Indeed, based ona survey conducted by PonemonInstitute in 2016, only 16% ofhealthcare and pharmaceuticalorganisations perform routinechecks and follow systematicmonitoring processes against cyberthreats. Furthermore, only 34% ofthe respondents reported that theyhave the necessary tools to performcyber threat monitoring, whereas29% indicated they have theresources to alleviate these threats.Finally, only 26% of the healthcareand pharmaceutical respondentsasserted that they have thecapabilities to examine andcomprehend these threats9.These findings emphasise the

necessity for investing in cybersecurity and demonstrate the easeof breach of access within the chainof data sharing, as not allpharmaceutical companies are ableto monitor and fight cyberattacks.In addition, pharmaceuticalcompanies often merge with other

CYBERATTACKS ON THEPHARMA INDUSTRYby Dr Nicola Davies

Acyberattack is defined as the “deliberateexploitation of computer systems, technology-

dependent enterprises and networks”1. In other words,it involves an intentional attempt by hackers to infiltrateand impair a computer network or system. Cyberattacksusually involve breach of access in terms of blocking useraccess and causing disruption of services. Such attackscan lead to cybercrime, which involves identity theft,data alteration, money theft, password loss, malwarevirus, and other malicious consequences1.

Dr Nicola Davies is a psychologist and freelance writer with a special interest in thehealth and pharmaceutical industry. She has written for over 100 magazines in 10countries. You can follow her work on Twitter (@healthpsychuk) or sign up to her freeblog https://healthpsychologyconsultancy.wordpress.com/

12 european INDUSTRIAL PHARMACY June 2017 • Issue 33

companies or are procured by morepowerful brands. These companieshave often suffered from hackers’attacks, as the confidentialinformation regarding a merger or aprocurement before becomingknown can be used for profit in thestock market10.

The impact of cybercrime inpharmaceutical companiesOne of the crucial aftermaths ofcyberattacks in pharma is a loss ofincome, as IP and research anddevelopment (R&D) processes arehighly costly. It has been estimatedthat the consequences ofcybercrime costs the UKpharmaceutical industry at least £27billion per year11. Furthermore, in aglobal analysis survey ofcybercrime, conducted by thePonemon Institute and comprising237 companies in six countries, itwas calculated that the annual costof cyberattacks for thepharmaceutical industry reachedalmost $5 million in 2016 (seeFigure 1)12,13.

Theft of IPIP constitutes the basis on whichthe R&D of new treatments anddrugs is constructed. IP is vital inimproving patient’s lives,promoting innovation, increasingcompetitiveness, andconsolidating the growth of thecompany. Biopharmaceutical IPinvolves patient data, drugpatents, molecular formulae,production processes, andcompliance data, among others13.It is estimated that the cost ofdeveloping a profitable drug cansurpass $2.6 billion per year,mainly due to technical, regulatoryand financial challenges associatedwith R&D procedures14. IPembezzlement provides thecybercriminal and the impropercompetitor to bypass the risks andcosts involved with R&D pipelinesand directly develop an effectiveand successful drug15. In particular,there are three main data domainswhich are most valuable tohackers.

• Clinical trial data, as this typeof information is not onlypatient sensitive, but alsoprovides commercialadvantage.

• Company inside informationand confidential dataregarding drug development.

• Drug pricing policies andmarketing strategies. Thistype of data offers an unfairadvantage to thecybercriminal, as cleverlyimplemented market launchstrategies are highlybeneficial against stricthealthcare budgets16.

Breach of access due tocyberattacks does not only result indata confidentiality issues (patients’medical data becomes known), butalso in data integrity problems(patients’ medical data becomesaltered)16. Organisations, but alsoindividuals, can pursue lawsuits onthe grounds of negligence andbreach of IP confidentiality. Thisimplies costs for attorney fees, courtcases, and also fines for lack ofregulatory compliance17.

Sequential consequencesBreach of confidential data can alsolead to prosecution, which not onlyharms the company financially, butcan also damage its image andreputation. These cyberattacks hurtthe prestige of pharmaceutical

companies, resulting in damagingcustomer relationships andmarketing catastrophe. Rebuilding acompany’s reputation and gainingpeople’s trust again requiressignificant spending on publicrelations and communicationapproach strategies17. A cyberattack implies impairment

or impediment of operations,constituting another economicburden related to cybercrime.Technical examinations are vital toidentify faults in security controls,and investment in stringent andnewer cyber security measures arealso crucial; the implicationsassociated with failing to employthese safeguards include furtherfinancial impact on the affectedpharmaceutical companies18. Litigations can also lead to

pharma companies being requiredto re-run clinical trials. Besides theeconomic implications of designingand launching clinical trials again,the setback of timely access toessential medicine may be at thecost of human lives18.

What are the necessarysteps to be taken againstcyberattacks?The cybercrime affecting the NHSand the various cyberattacks thathave taken place in the last fewyears pose a real challenge forpharmaceutical companies.Fortunately, however, there are

CYBERATTACKS ON THE PHARMA INDUSTRY continued

Figure 1. Average annualised cost by industry sector16.

13european INDUSTRIAL PHARMACY June 2017 • Issue 33

some vital steps companies cantake to protect their data.

1. Apply more rigid accesscontrols. This measureinvolves authenticating userswith the Risk-BasedAuthentications system,employing more difficultpasswords, reducingprivileged access and limitingaccess to unstructured data.

2. Raise cyber security awareness.This step relates to all IT staffemployed by pharmaceuticalcompanies, as they should beinformed about the latestupdates in security solutionsand be able to report apotential malware infectionand better identify dubiousactivities.

3. Reassess security controls. Theoutdated IT systems used bypharma need to be updatedwith new security controlsagainst Internet threats, suchas installing firewalls,extending risk assessments,and ensuring regular updatesin security systems.

4. Focus on data protection.More emphasis must beplaced on effective dataencryption, especially whendealing with medical recordsand other sensitive patientdata19.

5. Invest in cyberattackprevention. This includes dataleak detection resources.Also, previous hackingattempts and attacks shouldbe closely monitored as theycan occur again.

6. Create a cybercrime analyticsprogramme. This involvesconstructing a softwareprogramme which will notonly scan for potential cyberthreats but will also collectand analyse information on allhackers’ crimes and presentthe results via meaningfuldata analytics19.

7. Security via regulation. Thepharmaceutical industry is

one of the highest regulatedsectors and needs to complywith various laws andprocedures. The US Food andDrug Administration (FDA) 21CFR Part 11 is one of themost relevant regulations, asit demands from thepharmaceutical companies toapply monitoring, reviewingof older documentations,electronic audit controls, anddetermining weak points inthe security systems whendealing with electronicpatient records. Thus, strictcompliance to this FDAregulation will ultimatelyresult in better cybersecurity19.

Cyberattacks are not random acts,but well-thought-out andthoroughly planned violations.Although the consequences areserious for all industries, forpharmaceutical companies they arepotentially even more severe, ascybercrime can result in theendangerment of human lives.Regardless of whether the motivesbehind the cyberattacks arefinancial or strategic, these threatsneed to be monitored, scrutinised,and prevented. Investing in robustcybercrime security and raisingawareness are essentialmeasurements to be taken to avoidvulnerabilities, potential loss ofincome, and marketing catastrophe.

References1 Techopedia. Definition – What is acyberattack? Techopedia Inc.; 2107.Available at:https://www.techopedia.com/definition/24748/cyberattack

2 Shukla A. Pharma CIOs worry of cyber-attacks, reviving security infrastructure.Uttar Pradesh, India: ETCIO.com; 8August 2014. Available at:http://cio.economictimes.indiatimes.com/news/digital-security/pharma-cios-worry-of-cyber-attacks-reviving-security-infrastructure/39889360

3 Contos B. Cyber threats andpharmaceuticals. CSO 17 June 2016.Available at:http://www.csoonline.com/article/3084655/security/cyber-threats-and-pharmaceuticals.html

4 Palnitkar U. Rising spectre of cybercrimein the pharmaceutical sector. TheEconomic Times 13 February 2016.Available at:http://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/rising-spectre-of-cybercrime-in-the-pharmaceutical-sector/articleshow/50973680.cms

5 Rivett C, Namiluko C. Cyber security inpharmaceuticals. EuropeanPharmaceutical Review 22 October 2015.Available at:https://www.europeanpharmaceuticalreview.com/35994/news/blog/cyber-security-in-pharmaceuticals/

6 Miller J. Big Pharma's bet on Big Datacreates opportunities and risks. ReutersTechnlogy News 26 January 2016.Available ay:http://www.reuters.com/article/us-pharmaceuticals-data-idUSKCN0V41LY

7 Shohet, Y. How cyber criminals coulddestroy a company, or an industry.Pharmaceutical Processing 2016;September/October:10–11. Available at:http://digital.pharmpro.com/pharmaceuticalproducts/september_october_2016?pg=10#pg10

8 Seals T. Dragonfly/Havex targetingpharmaceutical sector. InfosecurityMagazine 29 September 2014. Availableat: https://www.infosecurity-magazine.com/news/dragonflyhavex-targeting/

9 VirtuIT Systems. Healthcare & pharmacompanies least prepared for cyber-attacks. Nanuet, NY, USA: VirtuIT; 25 July2016. Available at:http://www.virtuitsystems.com/single-post/2016/07/25/Healthcare-Pharma-Companies-Least-Prepared-for-Cyber-Attacks

10 Klubenspies L. 5 facts about cybersecurity for pharmaceutical companies.McLean, VA, USA: Booz Allen Hamilton;2016. Available at:https://www.boozallen.com/content/dam/boozallen_site/ccg/pdf/thought_p/5-facts-about-cyber-and-pharma.pdf

11 Cooper L. Why the pharmaceuticalindustry is so vulnerable to cyber-attacks.Electronic Specifier 21 September 2017.Available at:http://www.electronicspecifier.com/blog/why-the-pharmaceutical-industry-is-so-vulnerable-to-cyber-attacks

12 Ponemon Institute. 2016 cost ofcybercrime study & the risk of businessinnovation. Traverse City, MI, USA:Ponemon Institute; 2016. Available at:http://www.ponemon.org/local/upload/file/2016 HPE CCC GLOBAL REPORT FINAL3.pdf

13 PhRMA. Intellectual Property. Washington,DC, USA: PhRMA, retrieved 7 June 2017.Available at:http://www.phrma.org/advocacy/intellectual-property

CYBERATTACKS ON THE PHARMA INDUSTRY continued

14 european INDUSTRIAL PHARMACY June 2017 • Issue 33

CYBERATTACKS ON THE PHARMA INDUSTRY continued

14 International Federation of PharmaceuticalManufacturers & Associations. ThePharmaceutical Industry and GlobalHealth: Facts and Figures 2017. Geneva,Switzerland: IFPMA; 2017, p.8. Availableat: https://www.ifpma.org/wp-content/uploads/2017/02/IFPMA-Facts-And-Figures-2017.pdf

15 Maruyama M, Mahmood A, Roth W,Matsuo J, Boettcher C. Cyber & InsiderRisk at a Glance: The PharmaceuticalIndustry. New York City, NY, USA:Deloitte; 2016. Available at:https://www2.deloitte.com/jp/en/pages/life-sciences-and-healthcare/articles/ls/cyber-security-ls.html

16 Davenport H, Hanet J, Duxburry P. Whycombatting cyber-crime is critical for lifescience companies. Lexology 27 April2017. Available at:http://www.lexology.com/library/detail.aspx?g=7df4ab9e-45de-472e-bdc7-ab310068a47a

17 Barry F. Ex-homeland security cyber chiefwarns of threats to pharma. In-PharmaTechnologist 17 June 2015. Available at:http://www.in-pharmatechnologist.com/Regulatory-Safety/Ex-Homeland-Security-cyber-chief-warns-of-threats-to-outsourcing-firms

18 Deloitte. Deloitte identifies 14 businessimpacts of a cyberattack. New York City,NY, USA: Deloitte; 15 June 2016.Available at:https://www2.deloitte.com/us/en/pages/about-deloitte/articles/press-releases/deloitte-identifies-14-business-impacts-of-a-cyberattack.html

19 Martin S. We have no choice. We MUSTmake 2017 the year of cybersecurity. ITSPMagazine 2017. Available at:https://itspmagazine.com/from-the-newsroom/we-have-no-choice-we-must-make-2017-the-year-of-cybersecurity

PharmacoVigilanceRevıewJournal on drug safety issues

Editor – Rob BegnettThis quarterly journal provides informed commentand analysis of international pharmaceuticalregulations relating to the safe use of medicines andmedicinal devices. It also carries reviews of currentmethods of pharmacovigilance.

Order online at www.euromedcommunications.comOr email: publisher@euromedcommunications.com

Tel: +44 (0)1428 752222 Fax: +44 (0)1428 752223

PharmacoVigilanceRevıewSupporting the safe use of

medicines and medical devices

Managing Reference SafetyInformation

The EU centralised applicationfrom a pharmacovigilance andrisk management prospective

Post-authorisation aggregatesafety reporting: the new PSUR

New European pharmacovigilancelegislation – an adequateresponse to current challenges?

Volume 7 Number 3/4 Nov 2013

CALL FOR ARTICLESDear ColleagueWe hope you enjoy the european Industrial Pharmacy and find it both useful andinformative. We are currently seeking new articles for future issues of the journal and would like toinvite you to contribute an article or review paper on any aspect of industrial pharmacy tothe journal. All issues of european Industrial Pharmacy are indexed by both Scopus andEmbase and thus are available through the listings for any other industrial pharmacistinternationally.Please contact the Managing Editor, Phoebe Speis (foibhspeis@yahoo.co.uk) for furtherinformation or submissions.

15european INDUSTRIAL PHARMACY June 2017 • Issue 33

regulatory reviewThe current review periodhas seen a number ofchanges in the regulation ofmedicines and regulatoryguidance in the EU,International markets andthe USA.

USAFrequently asked questions(FAQs) – USA/EuropeanUnion (EU) MutualRecognition Agreement(MRA)The US Food and DrugAdministration (FDA) has publisheda very helpful set of 12 FAQs dated2 March 2017 on the recentlyannounced Decision No 1/2017 ofthe Joint Committee establishedunder Article 14 of the Agreementon Mutual Recognition between theEuropean Community and theUnited States of America, of 1March 2017 amending the 1998Sectoral Annex for PharmaceuticalGood Manufacturing Practices(GMPs), in particular its Article 14and Article 21.

Burkholderia cepacia complexposes a contamination risk innon-sterile, water-based drugproductsThe FDA advises drug

manufacturers of non-sterile, water-based drug products that there havebeen recent product recalls due toBurkholderia cepacia complex (BCC)contamination. BCC and otherwater-borne opportunisticpathogens are among thecontaminants that can be found inpharmaceutical water systems.BCC survive or multiply in a variety

of non-sterile and water-basedproducts because it is resistant tocertain preservatives andantimicrobial agents. Detecting BCCbacteria is also a challenge andrequires validated testing methodsthat take into consideration theunique characteristics of differentBCC strains.People exposed to BCC are at an

increased risk for illness or infection,especially patients withcompromised immune systems.Specifically, the FDA is reminding

drug manufacturers of six specificmeasures to take, with specificreferences to legal requirements foreach as detailed in 21 CFR 211 and21 CFR 314.

Modernising the way drugs aremade: a transition tocontinuous manufacturingRecent advances in manufacturingtechnology have prompted thepharmaceutical industry to considermoving away from batchmanufacturing to a faster, moreefficient process known ascontinuous manufacturing. The FDAis taking proactive steps to facilitatethe drug industry’s implementationof emerging technologies, includingcontinuous manufacturing, toimprove product quality and addressmany of the underlying causes ofdrug shortages and recalls.The Center for Drug Evaluation

and Research’s Office ofPharmaceutical Quality EmergingTechnology Program addresses notjust continuous manufacturingtechnologies, but also otheradvances like 3D printing, noveldosage forms, and novel containersystems. Under this program, theFDA engages with industry early inthe process of developing newtechnology, and discusses anyanticipated regulatory or scientificissues that may be part of a futureapplication.

Use of Nucleic Acid Tests toReduce the Risk ofTransmission of West Nile Virusfrom Living Donors of HumanCells, Tissues and Cellular andTissue-Based Products(HCT/Ps) – Guidance forIndustryThis guidance finalises the draftguidance dated December 2015 (80FR. 77645). The finalised guidanceprovides establishments that makedonor eligibility determinations fordonors of HCT/Ps, with

recommendations for testing livingdonors for West Nile Virus (WNV)using an FDA-licensed donorscreening test. The FDA believesthat the use of an FDA-licensednucleic acid test will reduce the riskof transmission of WNV from livingdonors of HCT/Ps and, therefore,recommends its use to test livingdonors of HCT/Ps for evidence ofinfection with WNV as set forth inthis guidance. This guidance doesnot provide information regardingtesting of cadaveric HCT/P donorsfor WNV.

Providing RegulatorySubmissions in ElectronicFormatThe version of this guidance postedon 5 May 2015 provided a timetableof 24 months after issuance of thefinal guidance for the initialimplementation of the electronicsubmission requirement for newdrug applications (NDAs),abbreviated NDAs (ANDAs),biological licence applications(BLAs), and master files, and 36months for commercialinvestigational new drugs (INDs).The timetable indicated that NDAs,BLAs, ANDAs and master files wereto be submitted electronically inelectronic common technicaldocument (eCTD) format starting on5 May 2017 (5 May 2018 forcommercial INDs). The FDA hasdetermined, in response to industrycomments and internal review, thatit is appropriate to extend therequired date to submit master filesin eCTD format by 1 year to 5 May2018. Among other factors, the FDArecognises that there have beenchallenges with submission ofmaster files in eCTD format, andeCTD uptake data for master files,in particular, indicated that adheringto the 5 May 2017 date could haveled to high rejection rates of masterfiles and thus slower FDA reviewprocesses, and, therefore, potentialunnecessary delay in the review ofsome drug applications. Thisguidance has been revised to reflectthis updated timetable.

16 european INDUSTRIAL PHARMACY June 2017 • Issue 33

REGULATORY REVIEW continued

Guidance for Industry –Hypertension Indication: DrugLabeling for CardiovascularOutcome Claims This final guidance is intended toassist applicants in developinglabelling for cardiovascular outcomeclaims for drugs that are indicatedto treat hypertension. With fewexceptions, current labelling forantihypertensive drugs includes onlythe information that these drugs areindicated to reduce blood pressure;the labelling does not includeinformation on the clinical benefitsrelated to cardiovascular outcomesexpected from such blood pressurereduction. However, blood pressurecontrol is well established asbeneficial in preventing seriouscardiovascular events, andinadequate treatment ofhypertension is acknowledged as asignificant public health problem. The FDA believes that the

appropriate use of these drugs canbe encouraged by making theconnection between lower bloodpressure and improvedcardiovascular outcomes moreexplicit in labelling. This guidancerecommends standard labelling forantihypertensive drugs exceptwhere differences in labelling aresupported by clinical data. The FDAencourages applicants to submitlabelling supplements containingthe new language.

USP General Chapters <659>,<661.1> <661.2> Packagingand Storage RequirementsThe purpose of the revisions is toprovide, through General Chapter<659>, a 3-year period forimplementation of the requirementsspecified in General Chapters<661.1> and <661.2>, whichotherwise would have becomeapplicable on 1 May 2017; toreinstate requirements previouslyexpressed in General Chapter<661> during this 3-year period; toenable early adoption of therequirements in General Chapters<661.1> and <661.2> at any timeduring the 3-year period in lieu ofmeeting the reinstated <661>requirements; and to remove the

exemption to General Chapter<661.1> for previously approvedpackaging systems.

EuropeEuropean Medicines Agency(EMA)EU and US MRA – regulatorsagree on mutual recognitionof inspections of medicinesmanufacturersRegulators in the EU and the UShave agreed to recogniseinspections of manufacturing sitesfor human medicines conducted intheir respective territories on bothsides of the Atlantic. The agreementwill enable both the EU authoritiesand the US FDA to make better useof their inspection resources to helpthem to focus on other parts of theworld where active pharmaceuticalingredients (APIs) and medicines forthe EU or US markets aremanufactured.The agreement is underpinned by

robust evidence on both sides ofthe Atlantic that the EU and the UShave comparable regulatory andprocedural frameworks forinspections of manufacturers ofhuman medicines. Teams from theEuropean Commission, EU nationalcompetent authorities, the EMA andthe US FDA have been auditing andassessing the respective supervisorysystems since May 2014, and haveworked closely together to reachthis agreement. The agreement is an annex to the

EU–US MRA which was signed in1998 but is not yet implemented.Many provisions of the agreementhave already entered into force andothers will enter into force on 1November 2017. By that date, theEU will have completed itsassessment of the FDA and theFDA is expected to have completedits assessment of at least eight EUMember States, and will begradually expanded to all MemberStates. Readers should note that Article 9

of the MRA states in respect ofbatch testing “In the EU, asprovided in Article 51 paragraph 2of Directive 2001/83/EC and in

Article 55 paragraph 2 of Directive2001/82/EC, the qualified personwill be relieved of responsibility forcarrying out the controls laid downin Article 51 paragraph 1 ofDirective 2001/83/EC and in Article55 paragraph 1 of Directive2001/82/EC provided that thesecontrols have been carried out inthe United States, the product wasmanufactured in the United Statesand that each batch/lot isaccompanied by a batch certificate(in alignment with the WHOcertification scheme on the qualityof medicinal products) issued by themanufacturer certifying that theproduct complies with requirementsof the marketing authorisation andsigned by the person responsiblefor releasing the batch/lot.”(In the past, I led the European

Federation of PharmaceuticalIndustries and Associations WorkingParty on these MRAs. It was so veryfrustrating to see the EU/USA MRA“kicked into touch” whilst theothers progressed. I sincerely hopethat the UK will be able to makearrangements post Brexit tocontinue with all the MRAs madewhilst it was a member of the EU –MH.)

EMA and heads of nationalcompetent authorities discussconsequences of BrexitThe goal was to start discussing howthe work related to the evaluationand monitoring of medicines will beshared between Member States inview of the United Kingdom’swithdrawal from the EU.Although negotiations on the

terms of the UK's departure havenot yet officially commenced andone cannot prejudge their outcome,work will now start on the basis ofthe scenario that foresees that theUK will no longer participate in thework of the EMA and the Europeanmedicines regulatory system as of30 March 2019.General principles for workload

distribution will include:

•ensuring business continuity;•maintaining the quality and

17european INDUSTRIAL PHARMACY June 2017 • Issue 33

robustness of the scientificassessment;

• continuing to comply with legaltimelines;

•ensuring knowledge retention,either by building on existingknowledge, or throughknowledge transfer;

• assuring an easyimplementation and medium-and long-term sustainability.

A follow-up meeting will take placeon 5 July 2017.

Brexit – notice to marketingauthorisation holders (MAHs)of centrally authorisedmedicinal productsUnless the withdrawal agreementestablishes another date or theperiod is extended by the EuropeanCouncil in accordance with Article50(3) of the Treaty on EuropeanUnion, all Union primary andsecondary law ceases to apply tothe United Kingdom from 30 March2019, 00:00h (CET). The UnitedKingdom will then become a ‘thirdcountry’. In this regard, MAHs ofcentrally authorised medicinalproducts for human and veterinaryuse are reminded of certain legalrepercussions, which need to beconsidered.

•EU law requires that MAHs areestablished in the EU (orEuropean Economic Area(EEA)).

•Some activities must beperformed in the EU (or EEA),related for example topharmacovigilance, batchrelease, etc.

Preparing for the withdrawal is,therefore, not just a matter forEuropean and nationaladministrations, but also for privateparties. MAHs may be required toadapt processes and to considerchanges to the terms of themarketing authorisation in order toensure its continuous validity andexploitation, once the UnitedKingdom has left the EU.

Questions and answers(Q&As) – UK withdrawal fromEU-medicinal products withinthe framework of theCentralised ProcedureThis first list of Q&As has beendrafted jointly by the EuropeanCommission and the EMA andconcerns information related toestablishment requirements withinthe EU (EEA). The Q&As will befurther updated and complementedin the near future. There arecurrently nine Q&As covering thefollowing.

•What if I am an MAHestablished in the UK?

•What if I am an orphandesignation holder establishedin the UK? (for medicines forhuman use)

•What if I am a UK company witha MUMS (Minor Use MinorSpecies/limited market) statusfor my product? (for veterinarymedicines)

•What if my qualified person forpharmacovigilance (QPPV)resides and carries out his/hertasks in the UK?

•What if my pharmacovigilancesystem master file (PSMF) islocated in the UK? (formedicines for human use)

•What if my manufacturing siteof the active substance islocated in the UK?

•What if my manufacturing siteof the finished product islocated in the UK?

•What if my batch release site islocated in the UK?

• I am a UK-based SME, would Istill have access to financial andadministrative assistance inaccordance with CommissionRegulation (EC) No 2049/2005(the ‘SME Regulation’)?

(A similar set of requirements couldwell apply to license holders basedin the EU for any product that theywish to export to the EU unless anMRA, some similar agreement, or a

transition arrangement is made. TheMedicines and Healthcare ProductsRegulatory Agency (MHRA) couldalso insist upon (or be legallyobliged to) inspecting EU-basedcompanies as was the case beforethe UK joined the EU. It may alsohave to inspect UK APImanufacturers to provide thenecessary assurances to the EUregulators as required in Q&A 6above. All despite the fact that EUand UK GMPs are aligned and likelyto remain so throughPharmaceutical InspectionCooperation Scheme (PIC/S)membership – MH.)

Report from the EMA–FDAquality-by-design (QbD) pilotprogramThe aim of this program was tofacilitate the consistentimplementation of QbD conceptsintroduced through InternationalCouncil for Harmonisation (ICH) Q8,Q9 and Q10 documents andharmonise regulatory decisions tothe greatest extent possible acrossthe two regions.Overall, it is concluded that, on

the basis of the applicationssubmitted for the pilot, there issolid alignment between bothAgencies regarding theimplementation of multiple ICH Q8,Q9 and Q10 concepts. TheFDA/EMA QbD pilot programopened up a platform forcontinuous dialogue which maylead to further communication onareas of mutual interest to continuethe Agencies’ support forinnovation and global developmentof medicines of high quality for thebenefit of patients. Both agencies are currently

exploring potential joint activitieswith specific focus on continuousmanufacturing, additional emergingtechnologies, and expedited/accelerated assessments (e.g.PRIME, Breakthrough). Additionally,the EMA and FDA are hostingexperts from each other’sorganisations to facilitate dialogueand explore further opportunities.

REGULATORY REVIEW continued

Question and Answers onImplementation of Risk BasedPrevention of CrossContamination in Productionand ‘Guideline on SettingHealth Based Exposure Limitsfor Use in Risk Identification inthe Manufacture of DifferentMedicinal Products in SharedFacilities’ There are 14 Q&As in this documentcovering several topics.

•Must health based exposurelimits (HBELs) be developed forall products? (Q1)

•What products/activesubstances are considered to behighly hazardous? (Q2)

•Could occupational exposurelimits (OELs) or occupationalexposure bands (OEBs) be usedto support assessment ofproducts to determine whetherthey may be highly hazardous?(Q3)

•Can calculation of HBELs bebased on clinical data only (e.g.to establish the HBEL on1/1000th of the minimumtherapeutic dose)? (Q4)

•How can limits for cleaningpurposes be established? (Q6)

•Where products for paediatricpopulations are manufactured inshared facilities with productsintended for administration toadults or to animals, do theHBELs need adjustment? (Q11)

Deadline for comments was 30 April2017. The MHRA has also publisheda guideline linked to the EMAdocument.

Reporting irregularities thatmay affect medicinesThe EMA Board has adopted a newpolicy on handling information onalleged improprieties from externalsources. These improprieties mayinclude allegations of departuresfrom standards of good practicesthat could have an impact on theevaluation and supervision ofmedicines.The goal is to create an

environment where individuals from

outside the Agency feel confident toraise their concerns on improprietiesin their area of work. The policyhelps the EMA assess these reportsand coordinate any furtherinvestigation in a structured way,while protecting the confidentialityof the reporter.

New EudraVigilance system forcollection and monitoring ofsuspected adverse reactionsThe EMA will launch a new andimproved version of EudraVigilance,the European information system ofsuspected adverse reactions tomedicines that are authorised orbeing studied in clinical trials in theEEA. The new version ofEudraVigilance will go live on 22November 2017 with enhancedfunctionalities for reporting andanalysing suspected adversereactions.Users of the system, i.e. national

competent authorities, MAHs andsponsors of clinical trials, have tomake final preparations to ensurethat their processes and localinformation technologyinfrastructure are compatible withthe new system and theinternationally agreed format.This EMA Management Board

endorsement starts the countdownfor stakeholders to get ready for thelaunch of the improved system inNovember 2017.

European Directorate for theQuality of Medicines (EDQM)Concept Paper on the Needfor Revision of Note forGuidance on Quality of Waterfor Pharmaceutical Use The current guideline needs to beupdated to reflect imminentchanges in the EuropeanPharmacopoeia (Eur. Ph.). The textof the guideline needs to beupdated to take into accountmanufacturing practices usingmethods other than distillation forproducing water of injectable qualityand the consequent deletion of themonograph “Water, highly purified”.A new Eur. Ph. monograph “Waterfor preparation of extracts” (2249) isalso published.

The objective of the guideline isto provide guidance to the industryon the pharmaceutical use ofdifferent grades of water in themanufacture of APIs and medicinalproducts for human and veterinaryuse. The intention of the revision isto be in line with the revised Eur. Ph.monograph for “Water for injections”(0169) and the consequent futuredeletion of the monograph “Water,highly purified” (1927). Commentswere due by 6 June 2017.

Test for abnormal toxicity:towards possible deletion fromthe Eur. Ph.The Eur. Ph. Commission is seekingpublic feedback on its proposal toremove the requirements for a testfor abnormal toxicity from 49monographs of the Eur. Ph. Thisconsultation will run until June 2017for all users, and will be extendeduntil August for NationalPharmacopoeia Authorities.

Top Ten Deficiencies – NewApplications for Certificates ofSuitability for Chemical PurityThis document is a summary of the10 most FAQs raised after the initialevaluation of new applications forcertificates of suitability (CEPs) forchemical purity. The top 10 FAQsare listed together with expectationsand recommendations on how toaddress the specific deficiencies,with reference to applicableguidelines. This document is intended to help

applicants to improve the quality oftheir dossiers, in order to facilitateand speed up the granting of theirCEPs. It should be taken intoaccount while building up a dossier,in combination with the EDQMguideline “Content of the Dossierfor Chemical Purity andMicrobiological Quality (PA/PH/CEP04 1)” available on the EDQMwebsite. The top 10 deficiencies areas follows.

•Absence or deficient discussionon the risk of having potentialmutagenic impurities in the finalsubstance.

REGULATORY REVIEW continued

18 european INDUSTRIAL PHARMACY June 2017 • Issue 33

REGULATORY REVIEW continued

19european INDUSTRIAL PHARMACY June 2017 • Issue 33

•Absence or insufficientdiscussion on fate and carryoverof related substances of startingmaterials to the final substance.

• Lack of details and/or poordescription of themanufacturing process of thesubstance from the introductionof starting materials

•Non-acceptable startingmaterials, necessity to redefinethem earlier in the process.

•Non-adequate or poorlyjustified specifications in placeto control the quality of startingmaterials.

•Non-adequate or missingspecifications (and analyticalmethods) for reagents andsolvents (recovered and recycledincluded) used to manufacturethe substance from theintroduction of startingmaterials.

•Non-adequate or missingdiscussion on carryover ofreagents and elementalimpurities to the final substance.

•Non-adequate or poorlyjustified specifications in placeto control the quality of isolatedintermediate.

•Absence or insufficientdiscussion on fate and carryoverof impurities from syntheticintermediates (included) to thefinal substance.

•Non-adequate or missinginformation on the synthesis ofstarting materials and theirmanufacturers.

Biosimilars: Eur. Ph.monographs are flexible andevolving standardsDuring a seminar co-organised withthe EMA, the EDQM clarified furtherthe role that the Eur. Ph.monographs play in the assessmentof biosimilars. As public standardsfor the quality of medicines inEurope, monographs ensure thequality of biosimilar and otherbiotherapeutic products, butcompliance with them is notsufficient for demonstrating

biosimilarity. However, while Eur. Ph.monographs provide specificationsin the form of tests and acceptancecriteria for all medicines, they aredynamic documents that can beadapted to scientific progress.Dr Peter Richardson, Head of

Quality at the EMA, providedinformation on EU legislation in thefield of biosimilars, and Dr NiklasEkman, Senior Researcher at theFinnish Medicines Agency sharedhis experience as an assessor.

Management of Applicationsfor New Certificates ofSuitability and Requests forRevisions or Renewal ofCertificates of SuitabilityPA/PH/CEP (13) 110, whichdescribed the policy for assessmentof CEP applications, has beenrevised following a review of currentpractice. As a result of the review, athree-round policy has beenadopted for the assessment ofapplications and this is reflected inthe revised document. This policy change reflects the

changing circumstances since theprevious policy was adopted, inparticular the increasingrequirements for applicants toredefine starting materials to anearlier point in the synthetic route.A similar policy is now applied to

the assessment of requests forrevisions/renewals of certificatesand, therefore, this is incorporatedin the revised document. Thedocument PA/PH/Exp. CEP /T (04)18, “Procedures for management ofrevisions/renewals of certificates ofsuitability to the EuropeanPharmacopoeia monographs” has,therefore, been withdrawn.

Co-ordination group for Mutualrecognition and decentralisedprocedures – human (CMDh)Q&A – qualified person (QP)declaration The CMDh of the Heads ofMedicines Agencies (HMA) hasrevised its Q&A document on theQP declaration. The update coversthe types of QP declarations thatmust be submitted to supportindividual changes to marketing

authorisations covering the QPdeclaration(s) required to supportindividual types of changes to amarketing authorisation, to confirmthat the active substance ismanufactured in accordance withthe detailed guidelines on GMP forstarting materials? Answers are given to cover the

different scenarios: APImanufacturer, finished productmanufacturer and batch release site.

MHRAMHRA GMP InspectionDeficiency Data Trend 2016The GMDP (good manufacturingand distribution practice)Inspectorate has improved the wayof gathering the inspectiondeficiency data for 2016. The newdata trending can allow industries toidentify the following.

•The severities and frequenciesby the EU GMP references.

•The overall number ofdeficiencies by categories:Critical, Major, Other.

•The high impact versus highfrequency issues.

The purpose for publishing theinspection deficiency data is to allowindustries to perform their ownassessment against the deficiencyfindings as part of self-inspectionand continuous improvement.

MHRA GDP Symposium 2016The MHRA has published asummary of this event on its blog.An exploration of company culturehighlighting the way individualsinteract, use processes and theeffect that this has on compliancewas the main theme. Topics coveredincluded the Falsified MedicinesDirective; whistleblowing andenforcement; error chains; and theDefective Medicines ReportingCentre.

Computer System Validation -GCPThis blog post is a combination of acase study seen at a singleorganisation and some of the

20 european INDUSTRIAL PHARMACY June 2017 • Issue 33

common findings good clinicalpractice (GCP) inspectors have seenacross a number of recentinspections.

Import of centrally authorisedmedicines for supply to otherMember States where themedicine is not yet availablein the correct pack The MHRA notes in this short blogthat occasionally it receivesnotifications for import of centrallyauthorised medicines for supply toother Member States where themedicine is not yet available in thecorrect pack for their market andwhere the Member State mayregard the supply to be intended tomeet special needs of individualpatients in the absence of anavailable licensed medicine.The MHRA will object to

notifications for import of anunlicensed medicine submitted inthis manner on the grounds that themedicine is in fact licensed andavailable. Consequently, it cannotbe notified for import as anunlicensed medicine.

Too much pressure: abehavioural approach to dataintegrity (part 2)Behavioural issues are oftenunsuitable for technical guidance,but the Inspectorate blog providesan opportunity to address thiscomplex issue.This second blog post of the

series illustrates the issues from thefirst in the series through a scenariobased on situations sometimesencountered during inspections,and the changes in organisationalapproach which can address someof the problems identified. PeterBaker, an investigator within FDA’sChina office based in Beijing, hasaddressed this issue during variousrecent industry workshops, includingthe 2016 International Data IntegrityWorkshop supported by regulatorsfrom the MHRA, the EDQM, theEMA, the China FDA, the US FDA,and the World Health Organization.This blog post summarises hispresentation and providesadditional insight into the concept

of “too much pressure” within apharmaceutical testing laboratory.(I would recommend the book

“Why Employees Don’t Do WhatThey’re Supposed to Do and Whatto do About it” [ISBN 0-07-134255-9]by Ferdinand F Fournies as excellentreading matter for management/trainers and operators on this topic– MH.)

InternationalPIC/S Reaffirmed stance onproposed EU advancedtherapy medicinal products(ATMP) GMP guidelines andgaps highlighted relating topatient safetyOn 24 April 2017, PIC/S sent a letterin response to a reply received fromthe European Commission on 5April 2017 in connection with PIC/S’stance on the proposed EU ATMPGMP guidelines, which it considerswill not only lower GMP standardsfor ATMP at the risk of patients butalso lead to an internationally non-harmonised approach to theimplementation of GMP for ATMP.In its latest letter, PIC/S reaffirms itsposition and highlights gaps relatingto patient safety, while welcomingthe Commission’s proposal forengagement with PIC/S on itsinitiative and seeking clarification onthe scope of cooperation proposed.

ProductsEMA recommends suspensionof medicines due to unreliablestudies from Micro TherapeuticResearch LabsThe EMA has recommendedsuspending a number of nationallyapproved medicines for whichbioequivalence studies wereconducted by Micro TherapeuticResearch Labs at two sites in India.The Agency also recommended thatmedicines not yet authorised butwhich are being evaluated on thebasis of bioequivalence studies fromthese sites should not be authoriseduntil bioequivalence is demonstratedusing alternative data.The review of medicines studied

by Micro Therapeutic Research Labs

was started after inspections tocheck compliance with GCP byAustrian and Dutch authorities inFebruary 2016. The inspectionsidentified several concerns at thecompany’s sites regardingmisrepresentation of study data anddeficiencies in documentation anddata handling.The review, by EMA’s Committee

for Medicinal Products for HumanUse (CHMP), concluded that datafrom studies conducted at the sitesbetween June 2012 and June 2016are unreliable and cannot beaccepted as a basis for marketingauthorisation in the EU.

EMA recommends changes toprescribing information forvancomycin antibioticsThe EMA has recommendedchanges to prescribing informationfor the antibiotic vancomycin toensure appropriate use in thetreatment of serious infectionscaused by Gram-positive bacteria,whilst ensuring appropriate use inthe fight against antimicrobialresistance. Vancomycin remains animportant therapeutic option for thetreatment of serious infections. TheAgency’s CHMP reviewed theavailable data and made thefollowing conclusions.

• Infusion of vancomycin cancontinue to be used for thetreatment of serious infectionscaused by certain bacteriaincluding methicillin-resistantStaphylococcus aureus inpatients of all ages.

•Vancomycin can also be used toprevent bacterial endocarditis inpatients undergoing surgeryand to treat infections inpatients undergoing peritonealdialysis.

•The starting dose of vancomycinby infusion should be calculatedaccording to the age andweight of the patient. Theupdated recommendations arebased on data which showedthat the previouslyrecommended dose oftenresulted in less than optimal

REGULATORY REVIEW continued

21european INDUSTRIAL PHARMACY June 2017 • Issue 33

levels of vancomycin in theblood, reducing theeffectiveness of the antibiotic.

•When taken by mouth, useshould be limited to thetreatment of Clostridium difficileinfections.

Because the available data do notadequately support the use ofvancomycin in the treatment ofstaphylococcal enterocolitis and itsuse to clear the gut of bacteria inpatients with a weakened immune(defence) system, the CHMPconcluded that vancomycin shouldno longer be used for theseindications. The CHMP opinion willbe forwarded to the EuropeanCommission, which will issue a finaldecision valid throughout the EU indue course.

FDA approves first cancertreatment for any solid tumourwith a specific genetic featureThe US FDA recently grantedaccelerated approval to a treatmentfor patients whose cancers have aspecific genetic feature (biomarker).This is the first time the agency hasapproved a cancer treatment basedon a common biomarker rather thanthe location in the body where thetumour originated.Keytruda (pembrolizumab) is

indicated for the treatment of adultand paediatric patients withunresectable or metastatic solidtumours that have been identifiedas having a biomarker referred to asmicrosatellite instability-high ormismatch repair deficient. Thisindication covers patients with solidtumours that have progressedfollowing prior treatment and whohave no satisfactory alternativetreatment options, and patients withcolorectal cancer that hasprogressed following treatment withcertain chemotherapy drugs.This is an important first; until

now, the FDA has approved cancertreatments based on where in thebody the cancer is – for example,lung or breast cancers. It now hasapproved a drug based on atumour’s biomarker without regardto the tumour’s original location.

Extending expiration dates ofdoxycycline tablets andcapsules in strategicstockpiles A number of government publichealth and emergency responsestakeholders maintain stockpiles ofdoxycycline tablets or capsules forpost-exposure prophylaxis ortreatment of inhalational anthrax inthe event of an anthrax emergency.States have asked the FDA whatwould be necessary to provideconfidence that stockpileddoxycycline tablets and capsuleshave retained their original quality(i.e. purity and potency) beyond themanufacturer’s labelled expirationdate so the replacement ofstockpiled product could bedeferred.This document, once finalised, will

provide guidance to governmentstakeholders on testing to extendthe shelf life (i.e. expiration date)under section 564A(b) of the FederalFood, Drug and Cosmetic Act ofstockpiled doxycycline tablets andcapsules for public health emergencypreparedness and responsepurposes for an anthrax emergency.

ConferencesEDQM Symposium onMicrobiology planned forOctober 2017The EDQM will hold an

international symposium on 10–11October 2017 in Strasbourg, Franceto present and discuss recentachievements, as well as futureperspectives, of the Eur. Ph. in themicrobiology field. The programmewill cover, among others, topics suchas rapid microbiology methods,including specific sessions onpharmaceutical water and celltherapy preparations; methods ofpreparation of sterile products; andbiological indicators used in themanufacture of sterile products.

DocumentsAssociation of BritishPharmaceutical Industries(ABPI) manifestoThe manifesto ‘Securing theOpportunity for UK Life Sciences by

2022’ sets out the industry’s threepriorities to improve the use ofmedicines and grow the UK’s statusas a global hub for life sciences andpharmaceuticals. The ABPI calls onthe next government to prioritisethe following.

•Securing a world-class NationalHealth Service (NHS) forpatients – a strategy to makepatient outcomes in the NHSthe best in the world. Thisshould start by increasinghealthcare investment to the G7average and ensuring the UK isin the top quartile ofOrganisation for Economic Co-operation and Developmentcountries for patient access tonew cost-effective medicinesand vaccines by 2022.

•Securing global investment andjobs – a new industrial strategythat cements the UK’s positionas a leading global hub for thelife science and pharmaceuticalindustry, attracting significantnew international investment.

•Securing a new relationship withthe EU that prioritises patientand public health – a newrelationship with the EU thatsecures patient access tomedicines and protects publichealth.

New Guide on BiosimilarMedicines for HealthcareProfessionals – IncreasingUnderstanding of BiosimilarMedicinesThe objective of the guidepublished jointly by the EMA andthe European Commission is toprovide healthcare professionalswith reference information on boththe science and regulationunderpinning the use of biosimilars.Biosimilars are biological medicinesthat are highly similar in all essentialaspects to a biological medicinethat has already been authorised.

EMA 2016 Annual Report The report focuses on the Agency’skey achievements in the areas ofmedicine evaluation, support to

REGULATORY REVIEW continued

research and development of newand innovative treatments and thesafety monitoring of medicines inreal life. In 2016, the Agencyrecommended a marketingauthorisation for 81 medicines forhuman use, including 27 new activesubstances. On the veterinary side,11 medicines were recommendedfor approval, including six newactive substances. Approximatelyhalf of the applicants who weregranted a positive opinion for theirmedicine had received scientificadvice from the EMA during thedevelopment phase of their product. The report also highlights some of

the EMA’s main projects, initiativesand achievements in 2016. These

include the launch of PRIorityMedicines (PRIME), an initiative tosupport the development ofmedicines that address unmetmedical needs and the policy on thepublication of clinical trial data fornew medicines, a ground-breakingnew initiative that turned the EMAinto one of the most transparentmedicines regulators worldwide.Other developments include theEMA’s contribution to addressingpublic health, includingantimicrobial resistance and the Zikavirus outbreak. The report also contains three

interviews on topics of majorinterest in the area of medicines andhealth in 2016.

•Vaccine hesitancy – a threat topublic health.

•Creating an agile organisationfor the 21st century.

•How to reinforce surveillance ofantimicrobial consumption.

For further information on theseand other topics, we suggest yourefer to the websites of relevantregulatory bodies and to currentand past editions of “GMP ReviewNews” published by EuromedCommunications. To subscribe tothis monthly news service contactinfo@euromedcommunications.com

22 european INDUSTRIAL PHARMACY June 2017 • Issue 33

Automated, Rapid

Environmental Monitor

ring.

he non-destructive test provides p T personne ,aterr, w,testing of surfaces

Direct™ System automates the hig Environmental monitoring through

Environmental Monitorinour Automate Y Your

e wth

positive . el and air .

gh volume the Grow

ng.

.monitoring cassettesbe configured to hold over 700 env

he two incu T.contamination eventslimits provide faster response to po

Configurable actio .sresults in CFU’uses no reagents for testing and pr

he sy Tmirrors the existing method. Sample prep .of traditional methods

results in hours and final results in

e about automating you o learn morTTo learn mor

tal an

rt

ime

vironment ubators ca

otential n and ale

ovides stem

paration half the t

a.rwww visit ,onmental monitoring ur Envir

p .comobiopidmicr

REGULATORY REVIEW continued

23european INDUSTRIAL PHARMACY June 2017 • Issue 33

PHARMA IN PLENARYThe rising costs of existingmedicines in Europeby Dr Nicola Davies

Rising costs of medicines inEuropean healthcaresystems is one of the majorconcerns for patients,advocates, governments,and other fundingorganisations that cover thecost of treatment. A reviewof the latest EuropeanParliament questions,positions, and declarationsrelating to industrialpharmacy shows thatincreasing medicine costsare observed in specifictherapeutic areas andwithin specific countries.This report provides asummary of the key issuesrelating to the rise in pricesof certain medicines and theactions being taken tocombat these issues.

The high cost ofcancer treatments1,2Cancer is one of the therapeuticareas where treatment prices haveskyrocketed in recent years. Aspecific aspect of this issue is thatsome drug makers increase theprices of cancer medicines that havelong been in the market and havelost their market exclusivity. Theprice of generic medicines, ideally,should be close to the productioncost. However, a few drug

manufacturers have increased theprice of generic cancer treatmentsover the last 5 years, with somedoing so by more than 1000%3. Forexample, Aspen PharmacareHoldings Ltd. increased the price forthe leukaemia generic drug,Busulfan, from 21 pence in 2011 to£2.61 in 2016. This is a 1143% priceincrease4. Another company,Actavis, has increased the cost oftheir hydrocortisone tablets by9500% from £1.07 to £102.743.

Aspen Pharmacare argued thatthe price increase was due to thefact that the generic drug, which hasbeen in the market for the last 60years, previously had a low-pricebase, which had stayed constantover the decades and has nowbecome unsustainable5. However,patient advocates are concerned forcancer patients who may lose accessto treatment due to “a desire forprofit”3.

Price differences forexisting medicines inthe Netherlands6The sudden increase in the pricesfor existing medicines is also anissue raised by pharmacists in theNetherlands. Specifically, newpharmaceutical organisations takeover the production of medicinesthat have existed in the market for along time and are still currently inuse, attaching a higher price tothese products. Dutch pharmacistsrefer to these drugs as “hijackedmedicines”7.Drug makers are not prohibited

from increasing medicine prices, butthe resulting scenario is that themedical insurance provider onlyreimburses the amount of theoriginal price. Therefore, the burdenof paying for the price differencefalls on the patient. In a questionposed to the European Commissionregarding this matter, theCommission was asked to considerwhether this pricing set-upconstituted a fair and honestmarket7.

The high cost ofmedicines in CyprusSoaring prices can also be morecommon in specific Europeancountries than in others. One suchcountry is Cyprus, which is identifiedas historically having high-priced

medicines that results in poor accessto treatment, especially forvulnerable segments of thepopulation. Many drugs are alsoimported from other countries andso high prices may be partly due tounfavourable foreign exchangerates8.Poor access to, and lack of

affordability in, medicines isconsidered a breach in thefundamental European Unionprinciple of equal and universalaccess to healthcare9. Therefore, theCommission is called upon toexamine the unique pricing situationin Cyprus.

Actions being takento combat risingcostsThe European Commission is takingsteps to address the various issuesof drug pricing that may negativelyimpact patients’ access to much-needed treatments.

An investigation into AspenPharmacare’s alleged excessivepricing10

A formal investigation into pricehiking concerns for five cancermedicines, including Busulfan, hasbeen opened. The company at thecentre of the investigation is AspenPharmacare, which acquired thecompanies that manufactured thesefive cancer drugs after theexpiration of the products’respective patent protectionperiods. This is the first Commissioninvestigation into a pharmacompany’s alleged excessive pricingpractice11.The Commission aims to find out

whether the company imposed“very significant and unjustifiedprice increases of up to severalhundred percent”, and whether thecompany used the price increase asleverage to threaten to withdraw the

24 european INDUSTRIAL PHARMACY June 2017 • Issue 33

PHARMA IN PLENARY continued

Visit the website: www.industrialpharmacy.eu for PharmaTV and Qualityby Design videos, Regulatory Review, Financial Pharma News and other

current items concerning Industrial Pharmacy

www.industrialpharmacy.eu

medicines from certain markets7.Specifically, the investigationfocuses on whether the companyacted in breach of the EU Antitrustrules, which penalise the impositionof trading and pricing practices thatcreate unfair conditions forcustomers11.

An initiative for informationexchange on health technologyassessment and pricing policies2

Regarding the question posed onwhat the Commission is doing tohelp regulate the rising prices ofcancer medicines, CommissionerVytenis Andriukaitis has providedthis response: “…the Commission ispromoting improved exchange ofinformation among Member Stateson their pricing policies to minimisenegative effects on the accessibilityof medicines and strengtheningtheir cooperation on a voluntarybasis; in particular through toolssuch as a European medicine pricedatabase (Euripid)”12.Andriukaitis added that the

Commission recently conducted apublic consultation, the aim of whichwas to drive an initiative to galvanisecooperation on health technologyassessment across Member Nationsand to share information and bestpractices for healthcare budgetsustainability12.

Promotion and support of priceregulating measures2

The Commission also emphasisesthe need for Member States toimplement measures, such as publicprocurement, promotion of genericand biosimilar use, and price-controlpolicies, which promote andstrengthen the accessibility,affordability, and cost-effective useof medicines. In addition, the

Commission has always shownsupport for authorities that facilitatenational competition whenever theyimpose fines on pharma companiesfound to have conducted unfairtrading practices and excessivepricing2.Appropriate and fair pricing is an

essential method to not only ensurethat patients have access to newtreatments, but also continuedaccess to existing medicines in themarket. The Commission maintainsthat measures to regulate medicineprices and secure the delivery ofcare remain key priorities ofMember States2.

References1 European Industrial Pharmacists Group.

Access to affordable and effective cancertreatments. European Parliament PharmaWatch. Paris, France: EIPG. Available athttp://eipg.eu/eurparlpharm/

2 European Industrial Pharmacists Group.Cost of cancer treatment. EuropeanParliament Pharma Watch. Paris, France:EIPG. Available athttp://eipg.eu/eurparlpharm/

3 Anderson M. Question for written answerto the Commission Rule 130. Cost ofcancer treatment. Brussels, Belgium:European Parliament, 20 February 2017.Available at:http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-%2f%2fEP%2f%2fTEXT%2bWQ%2bE-2017-000822%2b0%2bDOC%2bXML%2bV0%2f%2fEN&language=EN

4 Boseley S. Drugs firms are accused ofputting cancer patients at risk over pricehikes. The Guardian 28 January 2017.Available at:https://www.theguardian.com/society/2017/jan/28/nhs-drug-firms-cancer-patients-at-risk-prices-inflated

5 Kresge N, Paton J and Langreth R. OldCancer Drug Gets 1,227% Price Hike inFrugal U.K. Bloomberg 30 January 2017.Avaialble at:https://www.bloomberg.com/news/articles/2017-01-30/old-cancer-drug-gets-1-000-plus-price-hike-in-frugal-u-k

6 European Industrial Pharmacists Group.Petition on the replacement of a genericdrug with the original and the subsequentincreased cost therefore in theNetherlands. European Parliament PharmaWatch. Paris, France: EIPG. Available athttp://eipg.eu/eurparlpharm/

7 Gerbrandy GJ. Question for writtenanswer to the Commission Rule 130. Risesin prices of existing medicines in themedicines market. Brussels, Belgium:European Parliament, 24 March 2017.Available at:http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-%2F%2FEP%2F%2FTEXT%2BWQ%2BE-2017-002037%2B0%2BDOC%2BXML%2BV0%2F%2FEN&language=PL

8 Duzen Y. Exchange rates double the priceof medicines in TRNC. LGC News 21January 2017. Available at:http://www.lgcnews.com/exchange-rates-double-the-price-of-medicines-in-trnc/

9 Christoforou L. Question for writtenanswer to the Commission Rule 130. Highcost of medicines in Cyprus. Brussels,Belgium: European Parliament, 31 March2017. Available at:http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-%2f%2fEP%2f%2fTEXT%2bWQ%2bE-2017-002364%2b0%2bDOC%2bXML%2bV0%2f%2fEN&language=EN

10 European Industrial Pharmacists Group.Aspen Pharma’s anticompetitive practices.European Parliament Pharma Watch.Paris, France: EIPG. Available athttp://eipg.eu/eurparlpharm/

11 European Commission. Antitrust:Commission opens formal investigationinto Aspen Pharma's pricing practices forcancer medicines. Brussels, Belgium:European Commission, 15 May 2017.Available at: http://europa.eu/rapid/press-release_IP-17-1323_en.htm

12 European Parliament. Parliamentaryquestions. Answer given by MrAndriukaitis on behalf of the Commission.Brussels, Belgium: European Parliament, 7April 2017. Available at:http://www.europarl.europa.eu/sides/getAllAnswers.do?reference=E-2017-000822&language=EN

25european INDUSTRIAL PHARMACY June 2017 • Issue 33

Riding the WhirlwindCuriosityOur ability increases. Unexpectedtragedies increase. They seemyoked together. Thalidomide (1956–1961) messed with unborn bodiesand the minds and hearts of us all.Maybe tragedies are inevitablebecause “trial and error” is anessential part of the scientificmethod. The anthropologistEdmund Leach (1910–1989)observed that, “science offers ustotal mastery over our environmentand over our destiny, yet instead ofrejoicing we fell deeply afraid”.Imagine being feather dusterworms. We would whisk ourtentacles back into the safety of ourcases. However, being human, wecannot help exploring.The pharmaceutical industry

entangles itself in risky situations. Itboldly goes where nobody hasgone before. An example isdeveloping new drugs. Thesociologist Daniel Bell (1919–2011)stated that we cannot know whereinnovations will go.

RisksConsequences may be unintended.The kneejerk precaution of industryis some sort of insurance. Withoutit, much or all industry would halt.Some situations are highly novel.Then, risk is vastly greater. Anothersociologist, Ulrich Beck (1944–2015),noted that innovative pharmaceuticalcompanies face risks with threecharacteristics. Risks are of globalreach. Once an accident hasoccurred, they cannot go back.They cannot push some “undo”command as on some computer

software. Adverse consequenceshave no limit on time and space. One hazard hotspot with human

volunteers is Phase I clinical trials.One with adverse consequenceswas TGN1412, animmunoregulatory drug first trialedin 2006. Another was BIA 10-2474, ahuman cannabinoid systeminteractor, in 2016.Benefitting from the 20/20 vision

of hindsight, we know now that therisks were greater than anticipated.Humans are poor at objectivelyassessing the magnitude of risks orbalancing them. Some risks we feelintuitively are greater than they are.We seem to most fear those thathappen quickly and can graphicallyimagine. One example is crashingour vehicle over a precipice. Weconstruct guardrails there althoughtheir cost, if invested elsewhere,would increase safety more.Medicine package informationleaflets list side effects. Likelihoodsmay use absolute frequencies todivide into very common, common,rare and very rare. However, ifconsequences include a seriousdisease or death, objectiveassessment is unlikely.

SolutionsHow can the pharmaceuticalindustry protect against risk? It canuse various sorts of humaninteraction. The anthropologist AlanFiske (1947–) claims there are fourtypes. One is to adjust price in amarket. This needs money,technologies and mathematics. Thecapitalist pharmaceutical industrymust change sufficiently duringdrug patent periods. That recoups,at least, the costs of adverse

consequences. As businesses, theymust continue to make a profit.That demands rare and learnedexpertise. Good luck, if not a god-like foresight, also help. Another method is matching

exchanged gifts or bartering, tit-for-tat. Industry pays its human clinicaltrial volunteers. They presumablyponder risks before choosinginvolvement. However, volunteersare vulnerable. They deserve to befully informed. However, even themost able experts are uncertainabout the effect in healthy humansat that time — hence the trial.Society judges harshly any companyinflicting harm. A third method is that the

powerful confiscate. Thepharmaceutical industry seetheswith takeovers; the strong swallowthe weak including the lesspowerful company’s intellectualproperty, such as clinical trial data.The fourth method meritsconsideration in today’s uncertainworld of greater risks. Share profitsand risks without counting the cost.One strategy is cooperation withthe state or states somewhere on aspectrum. That includes followingguidance from the EuropeanMedicines Agency, collaborationwith academia and nationalisation.The latter seems unlikely. But so, wewere told, were Brexit or PresidentTrump.

Malcolm E Brown

bottled brown

General Assembly held inMalta 20–21 May During the General Assembly, AnniSvala (Suomen Farmasialiitto,Finland) was re-elected as Vice-President Education and Trainingand Giorgos Panoutsopoulos(Panhellenic Association ofPharmacists, Greece) was elected asVice-President Communications forthe next 3 years.The EIPG Past Presidents Award

was conferred on Jean PierrePaccioni, who was also declared anEIPG Fellow, while Valerie Lacamoirewas given the EIPG OutstandingService Award. The awards werecollected on behalf of bothawardees by EIPG Treasurer andFrench delegate Brigitte Saunier. Onbehalf of the Association in Ireland,Pharmacists in Industry, Educationand Regulatory, Helen Naddycollected the EIPG President’sAward for excellent support onwebinars, while on behalf of theItalian Association, AssociazioneFarmaceutici dell’Industria (AFI),EIPG Vice-President and Italiandelegate Piero Iamartino alsocollected the EIPG President’sAward for outstanding support andcommitment to EIPG shown by AFIthroughout the year. MichaelBittermann accepted an award forsponsorship on behalf of AesicaPharmaceuticals, Tricia Kennerly onbehalf of Walgreens Boots Allianceand Joanna Gatt on behalf of VivianCorporation.

Working Group on QualitySystems in SerialisationThe focus of this Working Groupwas on the implementation ofquality systems in serialisation, bothin manufacture and throughout thesupply chain. The licence holder is responsible

for the release of the product intothe market and, therefore, themarketing authorisation holder(MAH) must rely on themanufacturing site to perform arobust final step in the packagingprocess to produce a reliablebarcode system. The MAH must

ensure that the packaging materialis properly designed and approvedby the Competent Authority in orderto allocate the correct and readablebarcode to guarantee its traceabilityand reconciliation. The barcodegeneration and managementsystems should be able to interfacewith the systems adopted by anyon-boarding partners. The barcodemust be transferred in an approvedartwork that is sent to the packagingsupplier. The barcode can be pre-printed on each carton or adequatespace must be left for on-lineprinting. The packaging site mustensure that the supplier is fullyqualified to perform this work andbe in possession of the necessaryequipment and procedures to avoidany mix-up or mistake during eachstep in the process flow.At the packaging site, it is the

responsibility of the manufacturer toqualify and periodically assess thepackaging equipment’s performancein terms of reliability andrepeatability to ensure that it is ableto print, read and upload thebarcode, in the repository system, ofeach package available for thesupply chain. This last step is criticalbecause it is important to ensurethat all the information in thebarcode is completely transferred tothe repository system (data integrityaspects and big data management). During the packaging steps, the

quality system should ensure thatrejected, damaged and retainedsamples are not part of thecommissioning of the product and afinal reconciliation must beperformed to ensure that theseaspects were properly managed. Ifthe MAH assigns the packagingactivity to a third party contractmanufacturer, it is their duty toqualify and approve this supplier. Atechnical agreement needs to be inplace indicating the responsibility ofeach aspect impacting on the quality,safety and efficacy of the product,including anti-counterfeit measures,such as the unique identifier.Repackaging or relabelling of a

product already commissioned in

the repository system requires strictcontrol of the change in barcodebecause all the involved packs haveto be decommissioned andcommissioned again to trace thechange of code. In this case thereconciliation at the end of theprocess is strictly required. Points of reflection include the

recently revised Annex 16 of the EUGuidelines to Good ManufacturingPractice, which contains fewindications for addressing qualifiedpersons responsibilities in relation tothe Delegated Act and the impacton Annex 21, the new guidance forimporters of medicinal products.Also, the role and interaction withcountries that have MutualRecognition Agreements with theEU will need to be considered.

Working Group on Value-basedOutcomes in thePharmaceutical IndustryAs life expectancy in Europe israpidly increasing, what is certain isthat more and more people will beliving with a chronic disease,become susceptible to cancerand/or life-style/age-relatedconditions. The impact on society,the strain on healthcare systemsand the drive to provide innovativemedicines to improve standard ofcare cannot be underestimated andis leading to an unsustainablehealthcare model. Hence,expectations on the industry towork with government/regulatorybodies to demonstrate value-basedoutcomes is expected to rise andrise. Recommendations for EIPGfrom this working group are asfollows.

1. Increase/encourageinteraction betweenhealthcare practitioners andindustrial pharmacists.

2. Maximise continuingprofessional developmentopportunities.

3. Prepare a position paper onconnected data/precisionmedicine for submission tothe Commission.

news from the EIPG

26 european INDUSTRIAL PHARMACY June 2017 • Issue 33

27european INDUSTRIAL PHARMACY June 2017 • Issue 33

4. Work with the EuropeanAssociation of HospitalPharmacists and thePharmaceutical Group of theEuropean Union to put thepharmacist at the forefront ofpatient care whether it be inthe patients’ home or at thesurgery.

5. As waste is a key issue, itshould be discussed betweenpharmacists working incommunity, hospital andindustry and the Commission.

6. The pan-Europeaninfrastructure (as forpharmacovigilance) should beharnessed to supportevidence-based practice.

SymposiumA scientific symposium entitled“Precision Medicine: ParadigmShifts for Millennial Patients” washeld on the Friday before theGeneral Assembly. Dr PatriciaBonanno, a member of theManagement Board of theEuropean Centre for DiseasePrevention and Control and amember of the Horizon 2020Advisory Group on Nanotechnology,Advanced Materials, Biotechnologyand Advanced ManufacturingProcessing was the moderator. Theopening speaker was the Hon DrMiriam Dalli, MEP, who addressedthe audience via a recorded videomessage on the importance ofspecialist health matters, such asprecision medicine.Mr Martin Seychell, Deputy

Director-General for Health, DGSANTE, discussed access toinnovative medicines in the EU. Hementioned that the Commissionheld conferences in 2011 and 2016and that there had been a meetingon the applicable technologies in2013. Three billion euros havealready been spent on healthresearch and some of this is to alignand encourage capacity inpersonalised medicine. A policypaper about the management ofrare diseases has been completedby 126 academics and industrial

personnel. A number of proposalshave been put forward for improveddiagnosis and treatment of rarediseases involving 26 countries.State of the art technology isinvolved and expected to supportbetter patient outcomes. There is aneed for mobile health services anda renewed focus on access topersonalised health, including asecure infrastructure and interactionbetween digital health treatments toprovide equitable access tomedicines. He felt it was importantto build on sustainable action, toupdate achievements, avoidduplication, and to map forward to2020 where priorities will be set onhow and where we want to invest.Dr Barbara Freischem, Executive

Director, European BiopharmaceuticalEnterprises (EBE) within theEuropean Federation ofPharmaceutical Industries andAssociations (EFPIA) was the nextspeaker. She noted that we aremoving away from all patients being“all the same” and we need tounderstand the disease biology inorder to provide diagnoses. Thisprovides regulatory challenges for adiagnostic product marketedtogether with a medicinal product.There is limited patient access topersonalised medicine in Europeand there is a need for a Europeanframework supportive of emerginginnovation.The key regulatory challenges are

that Notified Bodies undertakechecks on diagnostics and whathappens if they disagree with theEuropean Medicines Agency (EMA)which has to register the medicinalproduct? How will labellingdecisions be coordinated betweenthe medicinal product and itscompanion diagnostic? A conceptpaper has been issued by the EMAand a workshop is planned. Aframework document explains howone can tease out patients for whomthe treatment will be beneficial. Theevolution of tests with multiplemarkers will lead to a patienttreatment pathway. Both the EFPIAand EBE are working on each of thechallenges that hamper

personalised medicines frombecoming a reality.Tricia Kennerly, Vice-President,

Walgreens Boots Alliance, discussedthe delivery to patients of precisionmedicines. Alliance Healthcare has390 distribution centres in 20countries and precision medicinesare expensive compared toconventional medicines. Therefore,an increase in working capital isneeded, new equipment andfacilities must be provided, the stockholding ability will alter and loss ordamage to the product will have tobe taken into account.Medicines innovation is driving

non-traditional models with patientaccess schemes for unlicensedproducts and unforeseen futurerequirements involving clinical andregulatory aspects. Handlingrequirements differ with specifictemperatures, fragile products,altered packaging, and handling ofsterile products, and new facilities,new equipment, specialist trainingand revised standard operatingprocedures will all be necessary. Shediscussed the Alcura cold chainvalidation needed for efficient andresponsive distribution ofbiomarkers and their drugtreatments. Patient supportincreases with a need for supportprogrammes, pharmacy versushome care delivery, adverse eventprofiles, new training, funding, batchrecall, labelling, tracking andtagging. Pharmacists will needtraining as there will be moreoutcome measurements, creatingentirely new big data sets. The last speaker was Dr Romina

Britta, a post-doctoral researchfellow from the University of Maltacurrently on a scholarship with theUniversity of St Andrews, Scotland.She is a specialist in molecularpathology, specifically in the field ofcolorectal cancer. Her area ofinterest is in basic and translationalresearch (data mining, patientcohorts and biobanks) towardsdevelopment of predictive andtheranostic biomarkers. Sheexplained precision medicine fromone size fits all towards medical

NEWS FROM THE EIPG continued

models that use molecular profiling.This can be from developing drugson the basis of “one gene, onedrug” to “multi-gene, multi-drug”models that establish which drug fitswhich patient at the highestefficiency. Biomarkers are diagnostic

products that can predict individualsat higher risk of developing adisease. Prognostic biomarkersindicate the likely progression of thedisease. In addition, there arepredictive and surveillancebiomarkers. Basic research hasshown the development of diseaseand translational research hasmoved from the bench to thebedside. Pre-clinical test mousemodels are cell-line derivedxenograft in vivo models. Organoidsas models may fill the gap betweencancer genetics and patient trials.She described one of thetechnologies “Clustered regularlyinterspaced short palindromic

repeats” (CRISPR) as a powerfulfunctional tool and “Complimentaryfunctional analysis”, such as imagecytometry for plate-based assays, asvery expensive. There is obvious improved clinical

impact with patient stratification,and biomarkers can inform clinicaldecisions. A new regulatoryenvironment will be needed as“systems medicine” is a way ofthinking. There needs to be morecollaboration and equalpartnerships between academia,industry and clinicians.In response to a question from

Gino Martini on “big data”, MartinSeychell agreed that we do notreally exploit data and that it waslittle used to optimise patienttreatment. The Commission areworking on a plan for digital healthand the need to standardise data.The problem has been thatGovernments have not been able toput data “on the table”, and there

needs to be greater trust betweenhealthcare systems and industry ondata ownership.In response to a comment from

Amon Wafelman on governmentmanufacturing sites, it was felt thatthe Commission should worktogether with Member States,define and adapt the tools and beflexible. New technologies areforcing us to face reality.In his closing remarks, Claude

Farrugia said that as “big data”important to patient care becomesavailable along the supply chain, weshould be considering accessibilityand “make haste withresponsibility”.The slides shown by Dr Frieschem

and Ms Kennerley during the aboveSymposium presentations areavailable on the EIPG website.

Jane Nicholson(jane@nicholj.plus.com)

NEWS FROM THE EIPG continued

28 european INDUSTRIAL PHARMACY June 2017 • Issue 33

29european INDUSTRIAL PHARMACY June 2017 • Issue 33

30 european INDUSTRIAL PHARMACY June 2017 • Issue 33

eventsJULY 20173–5 July 2017 – Bangkok, Thailand4th Annual Congress on DrugDiscovery & Designing http://drugdiscovery.pharmaceuticalconferences.com

10–11 July 2017 – Jakarta, Indonesia8th Global Pharmacovigilance &Drug Safety Summit http://globalpharmacovigilance.pharmaceuticalconferences.com/

10–12 July 2017 – Madrid, Spain9th Annual European PharmaCongress http://europe.pharmaceuticalconferences.com/

17–19 July 2017 – Munich, Germany9th International Conference andExhibition on Pharmacovigilance& Drug Safety http://pharmacovigilance.pharmaceuticalconferences.com/

24–25 July 2017 – Rome, Italy13th International Conference andExhibition on Nanomedicine andPharmaceutical Nanotechnology http://nanotechnology.pharmaceuticalconferences.com/

31 July–1 August 2017 – Milan, Italy3rd World Congress andExhibition on Antibiotics andAntibiotic Resistancehttp://antibiotics.pharmaceuticalconferences.com/

AUGUST 201717–18 August 2017 – Los Angeles,CA, USA8th Annual Global Pharma Summithttp://www.clocate.com/conference/8th-Annual-Global-Pharma-Summit-2017/62641/

31 August–1 September 2017 –Las Vegas, NV, USA5th International PharmacyConference http://pharmacy.pharmaceuticalconferences.com/

SEPTEMBER 20175–7 September 2017 – Hatfield, UK8th International PharmSciConference 2017www.apsgb.co.uk

7–9 September 2017 – Paris, France6th World Congress on Biopolymershttp://biopolymers.conferenceseries.com/

10–14 September 2017 – Seoul,Republic of Korea77th FIP World Congress ofPharmacy and PharmaceuticalSciences 2017http://www.fip.org/seoul2017/

11–13 September 2017 –Washington, DC, USAPDA/FDA Joint RegulatoryConferencewww.pda.org

20–21 September 2017 – Dublin,Ireland3rd International Conference onAdvanced Clinical Research andClinical Trials http://clinicalresearch.pharmaceuticalconferences.com/

25–26 September 2017 –Chicago, IL, USA6th International Conferenceand Exhibition on GMP, GCP &Quality Controlhttp://gmp-gcp-quality-control.pharmaceuticalconferences.com/

25–26 September 2017 –Chicago, IL, USA7th International Conferenceand Exhibition onPharmaceutical RegulatoryAffairs and IPR http://regulatoryaffairs.pharmaceuticalconferences.com/

25–27 September 2017 – Vienna,Austria3rd International Conferenceand Expo on Drug Discovery &Designinghttp://drugdiscovery.pharmaceuticalconferences.com

26–27 September 2017 – Dublin,Ireland2017 Europe BiotechnologyConferencewww.ispe.org

OCTOBER 20179–10 October 2017 – San Diego,CA, USA4th Annual Drug Discovery USACongresshttp://www.discoveryusa-congress.com/

10–11 October 2017 –Strasbourg, FranceEDQM Symposium onMicrobiologyhttps://www.edqm.eu/en/news/edqm-symposium-microbiology-planned-october-2017

10–11 October 2017 – Prague,Czech RepublicPharmaceutical Cold & SupplyChain Logisticswww.pda.org

10–12 October 2017 – Barcelona,SpainWorld Vaccines ConferenceEuropehttp://www.terrapinn.com/conference/world-vaccine-congress-europe/index.stm

16–17 October 2017 – SanFrancisco, CA, USA10th International Conferenceand Exhibition on Biologics andBiosimilars http://biosimilars-biologics.pharmaceuticalconferences.com/

16–18 October 2017 – Baltimore,MD, USA11th World Drug DeliverySummit http://drugdelivery.pharmaceuticalconferences.com/

16–18 October 2017 – Budapest,Hungary 12th World Pharma Congress http://world.pharmaceuticalconferences.com/

19–20 October 2017 – Seoul,Republic of Korea9th Annual Congress on DrugDesign & Drug Formulationhttp://drugformulation-bioavailability.pharmaceuticalconferences.com/