european industrial pharmacy issue 24 (march 2015)

ISSUE 24 • MARCH 2015www.industrialpharmacy.eu

www.eipg.eu

features4 INTERNATIONAL EFFORTS TO PROTECT

PATIENTS FROM UNSAFE PHARMACEUTICALSIndustry experts, law enforcement and regulatorswork globally to staunch the flow of dangerous,unregulated pharmaceutical products.by Jim Dahl, Thomas T. Kubic and Marv Shepard

8 GREEN ANALYTICAL CHEMISTRY IN THEPHARMACEUTICAL INDUSTRYA critical evaluation of the advantages of greenanalytical chemistry in the pharmaceutical industry.by Sergio Armenta and Miguel de la Guardia

11 PLANNING YOUR FIRST YEAR OF SELLING INTHE US LIFE SCIENCES MARKET European life science companies face manyhurdles to break into the US market, but withstrategic planning they can land on fertile soil.by Jim Worrell

13 THE POWER OF DRUG COLOURThis paper investigates the subtle ways in which adrug’s colour can improve its efficacy.by Tessa Fiorini Cohen

15 IRELAND LAUNCHES AN INTEGRATED 5-YEARPHARMACY EDUCATION AND TRAININGPROGRAMMEThis article outlines changes in pharmacyundergraduate education in Ireland with the fullyintegrated MPharm programme in September 2015. by Maura Kinahan

16 EPSA INDIVIDUAL MOBILITY PROJECTA long-term internship project giving opportunitiesto gain real-time work and research experience.by Svetlana Kolundžić

23 COMPETENCES FOR INDUSTRIALPHARMACY PRACTICE IN BIOTECHNOLOGY– THE PHAR-IN PROJECTThe PHAR-IN Consortium has produced andevaluated a biotechnology competenceframework identifying priorities in developing acourse to acquire such competences.by The PHAR-IN Consortium

regulars3 EDITORIAL COMMENT18 REGULATORY REVIEW20 BOTTLED BROWN21 NEWS FROM THE EIPG22 EVENTS

europeanINDUSTRIALPHARMACY

2 european INDUSTRIAL PHARMACY March 2015 • Issue 24

europeanINDUSTRIALPHARMACYIssue 24 March 2015

ISSN 1759-202X

MANAGING EDITORSue Briggs

PRODUCTIONDave Johnson

SUBSCRIPTIONSJill Monk

EDITORIAL BOARDMichael AnisfeldClaude FarrugiaMichael Gamlen

Linda HakesJohn Jolley

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

Cover photo: Pills with different hues (seeThe Power of Drug Colour on page 13).

associate editors

Belgium: Philippe Bollen

Bulgaria: Valentina Belcheva

Czech Republic: Ales Franc

Denmark: Marie Fog

Finland: Anni Svala

France: Jean-Pierre Paccioni

Germany: Armin Hoffmann

Great Britain: Shilpa Gohil, Janet Halliday

Greece: Ioannis Nikolakakis

Hungary: Sylvia Marton

Ireland: Stan O'Neill

Italy: Piero Iamartino

Latvia: Inta Saprovska, Anita Senberga

Malta: Claude Farrugia

Netherlands: Amon Wafelman

Norway: Wenche Gordon

Portugal: Nuno Moreira

Spain: Beatriz Artalejo

Sweden: Marianne Andersson

Switzerland: Valter Gianesello, Maurizio Battistini

A year of challenges,a year of workTime flies! It seems onlyyesterday that we were in Sofialistening to our guest speakers,and here we are already – at themoment in time when I have thegreat pleasure in looking forwardwith anticipation to seeing you allonce again soon in Edinburgh forour General Assembly on the18–19 April. Immense thanks goto the Royal PharmaceuticalSociety, and particularly to JanetHalliday, for offering to be our distinguished hoststhis year, and also for organising the ScientificSymposium on Friday 17 April at the University ofStrathclyde on Advances in Technology Impactingthe Pharmaceutical Industry.

Yes, it has been a year of challenges, to continueto target the objectives I committed myself towhen you gave me the honour of accepting me asyour President in Brussels. PHAR-IN, theemergence of biotechnology, participation in theEuropean Medicines Agency Interested Partiesforum, continuing to address medicines shortages,responsible transparency, the update to Annex 16 –all these we have worked on, as you will see whenwe meet at the General Assembly, and I must offermy heartfelt thanks to my colleagues on the Bureauand to others in the EIPG who have contributedtirelessly and selflessly to this hive of activity.

In particular, I would like to highlight the webinarrecently organised conjointly between theEuropean Pharmaceutical Students’ Associationand the EIPG at which Claude Farrugia andGeorgina Gal delivered well-received presentations

– so well received, in fact, that an“encore” was requested and dulyorganised. It represents but afraction of the renewed impetuswith which collaboration betweenthese two organisations has beenrediscovered over the past year,thanks to the energy and drive ofour Vice President for Educationand Careers, Anni Svala. This aspectof the EIPG activities is a key“raison d’être” of EIPG, for ourcommitment to industrialpharmacists is not limited to today’s

professionals, but also, importantly, to those ofyears to come. It is with this principle in mind thatEIPG continues to give due importance tointeraction with budding industrial pharmacists atits General Assembly and pre-assembly ScientificSymposium.

Yes! A year of challenges and a year of work, andnever a moment to rest on our laurels, as weprepare to proudly participate as an observer to theUS Pharmacopeia Convention in April 2015 inWashington. “Mais pas plus pour l’instant”. Therewill be time for that, and more, when we meet soon.

Welcome to Edinburgh!

Jean Pierre PaccioniEIPG President

3european INDUSTRIAL PHARMACY March 2015 • Issue 24

editorial

Visit the website: www.industrialpharmacy.eu for PharmaTV andQuality by Design videos, Regulatory Review, Financial Pharma News

and other current items concerning Industrial Pharmacy

www.industrialpharmacy.eu

The situation in 2013 The Pharmaceutical SecurityInstitute, which has collected dataon counterfeiting, illegal diversionand theft incidents for twelveconsecutive years, reported a rise incounterfeit drug incidents andillegal diversion incidents in 2013.The 2193 incidents ofpharmaceutical crime which werereported were a significant 8.7%increase over 2012 – the highestannual total ever documented.Among those incidents were 406illegal diversion cases, a 24%increase over 2012 (see Figure 1).

Reporting also showed changes inwhich medicines were being soldand how they were shipped.

Counterfeiters narrowed theirproduct lines from 523 different

medications in 2012 to 317 in 2013.They also moved back towardssending their products in largershipments. Of 1156 counterfeitingincidents involving medicinesobtained in either customs seizuresor police/health inspector raids, 526(46%) counterfeit medicine seizureswere “commercial” size. In 2012,only 40% of the 841 seizures were ofa commercial size.

Finally, there was an uptick inenforcement. Arrests of peopleinvolved in the counterfeiting, illegaldiversion and major thefts ofpharmaceuticals increased 18% to1460 this year. Arrests of thoseengaged in illegal manufacturingincreased 151%, reversing a 3-yeardownward trend. Sixty-three illegalpharmaceutical manufacturingfacilities (IPMFs) were detected in2013, an increase from 37 IPMFsfound last year. There were 426incidents where counterfeit productsreached licensed wholesaledistributors and/or pharmacies in 49different countries. This was adecrease of 12% from 2012 (seeFigure 2).

International cross-agencyeffortsSolving the counterfeit problemrelies fundamentally on internationalcross-agency efforts, and, in recentyears, we have strengthenedcommunication and coordinationacross the entire pharmaceuticalsupply chain.

Enforcement agencies combinedefforts to combat illegal medicinesin over 40 nations. According topublished reports, they made 2636

european INDUSTRIAL PHARMACY March 2015 • Issue 24

INTERNATIONAL EFFORTS TOPROTECT PATIENTS FROMUNSAFE PHARMACEUTICALSby Jim Dahl, Thomas T. Kubic and Marv Shepherd

The public and private sector, law enforcement andgovernment have worked to build relationships,

strengthen regulation and improve product packaging toprotect patients across the world from unsafe medicinesthat are trafficked by transnational criminalorganisations. Our efforts have had a significant impact,but the problem remains.

Jim Dahl is a subject matter expert in pharmaceutical crime and malicious producttampering with over 30 years of US federal law enforcement experience. Dahl served for9 years as Assistant Director of the US Food and Drug Administration's Office of CriminalInvestigation and in private industry as Global Product Security Director at Eisai CompanyLtd., as the principal of his own independent consulting company and as Senior ManagingDirector for Crisis Management at an international security consulting firm.

Thomas T. Kubic is President and CEO of the Pharmaceutical Security Institute (PSI), anon-profit association dedicated to protecting the public health by sharing informationand initiating investigations into unsafe medicines by the authorities. A former executivewith the FBI, he now represents the PSI at numerous international meetings, conferencesand seminars. The PSI’s collaborations include working with international and nationallevel authorities, including INTERPOL, the United Nations Office on Drugs and Crime andthe World Customs Organization. He is an officer with the Partnership for Safe Medicines,and serves as an advisor to the Permanent Forum on International Pharmaceutical Crimeand INTERPOL’s Pharmaceutical Industry Initiative to Combat Crime.

Dr. Marv Shepherd is Director of the Center for Pharmacoeconomic Studies andChairman of the Center for Pharmacoeconomic Studies College of Pharmacy Universityof Texas at Austin. Dr. Shepherd examines policies related to drug importation and re-importation (especially from Mexico), the use of drug anti-counterfeiting strategies andtechniques for monitoring prescription drug diversion. His research and expertise ondrug importation and counterfeiting has been featured in major media outlets in theUS. He also serves as President of the Partnership for Safe Medicines.

4

Figure 1: Diverted drugs. (Photograph courtesy of the US Federal Bureauof Investigation).

INTERNATIONAL EFFORTS TO PROTECT PATIENTS FROM UNSAFE PHARMACEUTICALS continued


arrests on a global basis and seizedmore than $757,000,000 in illegalmedicines. In May 2014, INTERPOLcoordinated Operation Pangea VI,an international action week againstillegal online sales of medicinesduring which 198 agencies seized9.8 million doses of medicines in 113countries and shut down 11,800websites. The World CustomsOrganization’s (WCO’s) OperationBIYELA 2 intercepted more than 113million illicit, counterfeit andpotentially dangerouspharmaceutical products at 15African ports.

Non-governmental organisations(NGOs) and the public sector havebeen active. Eight African nationstook steps ranging from jointoperations with the police andcustoms services to outright bans onthe importation and sales ofmedicines from certain countries.The International Federation ofPharmaceutical Manufacturers andAssociations was joined by tenmajor NGOs in a new program,‘Fight the Fakes,’ which wasdesigned to raise consumerawareness, a challenge identified bythe WCO. Pharmacist associationsreiterated the messages of drugregulators concerning the problem

of herbal medicines that containactive pharmaceutical ingredients,which, in the case of Nigeria,resulted in further complications inthe medical conditions of patients.

More private companies have alsojoined the effort. In February, Baidusigned a partnership agreementwith China’s Food and DrugAdministration to promote the safeacquisition of medicines over theinternet by providing credible druginformation online and shuttingdown sites that disseminate falseinformation. Teva, a genericmedicines manufacturer, publiclyreported working with theauthorities to disrupt a criminalorganisation working in fourEuropean countries1,2.

Legal reformsSignificant progress in improvinglegal structures and regulations hasbeen seen in 2013 and 2014 tobetter prevent and prosecutecounterfeit pharmaceutical crime.

The Council of Europe’sMedicrime Convention, whichestablishes a standard to prosecutecounterfeit medical products on apublic health basis, is gainingmomentum. At present, 20European states, as well as Guinea,

Israel and Morocco, have signed theConvention. It has been ratified byfour Council of Europe memberstates – Hungary, Spain, Ukraine andMoldova – and will take effect oncefive member states have ratified it.

The Convention creates a legalframework that makes themanufacture and sale of counterfeitmedicines and similar crimes illegalin and of themselves and a separateoffense from any intellectualproperty violation. It harmonisesdefinitions of criminal activityimpacting public health, promotescooperation and prevention/awareness activities betweenparties, and criminalises otheractivities often found hand-in-handwith counterfeit drugs. Theseinclude offering to or attempting tosupply illegal product; falsification ofa broad range of documents used inthese offenses; possession ofproducts, materials, accessories orfalsified documents with intent tocommit criminal acts; andintentionally placing products on themarket without authorisation. Itcovers medical devices in a similarfashion3.

In addition to the MedicrimeConvention, several countries havemade strides to improve theirregulation of the drug supply chain.The US Drug Supply Chain SecurityAct, which was signed in November2013, creates a national standardthat supersedes fragmented statelegislation by codifying theresponsibilities of supply chainactors to verify the licensing of theirtrading partners, label and trackpharmaceuticals, investigatesuspicious products, and shareinformation. In December 2013,Brazil passed a track and trace lawwhich provides for unit-levelserialisation and tracking throughoutthe entire drug supply chain4,5.

The European Union Directive2011/62/EU requires serialisation ofall salable products followed byauthentication of the serial numberat point of sale. The Directiveintroduced as a general rule thatmedicinal products subject toprescription should bear the safetyfeatures unless an assessment shows

Figure 2: Counterfeit drug incidents worldwide, by region, 2014. (Courtesyof the Pharmaceutical Security Institute).

the absence or limited risk offalsification, i.e. affixed safetyfeatures on outer packaging6.

Several countries have increasedpenalties for drug counterfeiters. InJuly 2014, Russia amended itscriminal code to raise the maximumpenalties for the production ofcounterfeit medication to 5 millionroubles ($150,000) and up to 12years in prison. Kenya and Ecuadorhave also passed reforms7.

Cross-agency/countrycooperationThe US Food and DrugAdministration (FDA) has extendedits international efforts to improveenforcement. In 2014, for the firsttime, an agent from the FDA’s Officeof Criminal Investigations (OCI) willbe assigned to Europol to moreeffectively carry out internationalinvestigations. The FDA continuesto work with INTERPOL oninvestigations and projects such asOperation Pangea VI8–10.

Fighting counterfeit drugswith packagingPharmaceutical companies areimproving drug packaging to resistthe efforts of counterfeiters. TheFDA has recommended thatpharmaceutical manufacturersprotect their products by using amultiple, periodically changing,layered approach with at least onecovert marker. Many companiestoday have responded byemploying three or more overt andcovert markers on drug packagingand some companies employproduct forensic markers.

Overt markersOvert markers on drug packagingare visible to the naked eye.Common overt methods includeholograms, colour-shifting inks,watermarks and raised printing.Some of these may appear on theproduct packing; others on productpackage inserts. Holograms arewidely used by many industries, notjust for pharmaceuticals. Todayholograms can be verysophisticated and some even havecovert markers inside the hologram,

along with embedded serialnumbers. Polychromatic inks, whichchange colour depending on theangle from which they are seen, arecommonly used as an authenticitymarker for many industries. Manynations, including the US, usecolour-changing inks on papermoney and this approach is acommon authenticity approach forpharmaceutical products. Forexample, Pfizer uses colour-shiftingink on Viagra® packaging. Anotherovert technique is the use ofwatermarks embedded on theproduct package insert or the labelmaterials. Lastly, embossed orraised printing is still beingemployed.

Covert markersCovert markers are packagemarkers which cannot be seen bythe naked eye. These includeinvisible inks, embedded micro-wires or magnetic threads andhidden computer chips. The mostcommon types of covert markersare invisible inks. Invisible inksrespond to different lightfrequencies and can only be readusing the correct light source. Themajor advantage of invisible inks isthat they can be printed on top ofvisible ink printing so that packagedesigners do not need additional“real estate” to use them. However,many companies employ invisibleinks on the inside of the packageand on closure flaps and covers. Tokeep counterfeiters at bay, somecompanies periodically change theinvisible ink colour and changewhere invisible ink appears onproduct packaging. Othertechniques such as magneticthreads and micro-wires hidden inthe packaging and labels can beread using a scanning device.Hidden computer chips placedbehind the product label or withinpackage material are becomingmore common. These chips, whichare commonly referred to as RFID(radio frequency identifier) chips,produce or reflect a radio signalwhich transmits a product’sauthentication identificationnumber to a nearby receiver.

Forensic markersPharmaceutical companies are usingtwo methods of forensic markers,taggants and nano-encryption.Taggants are very small amounts ofa chemical inert substance placedwithin the drug product. Becausethey are only known to the companymanufacturing a product, they act asa unique identifier and simplifyanalyses which can distinguishauthentic products from counterfeitproducts. The FDA has a long list ofapproved substances that can beused as product taggants.

Another form of forensic marker,nano-encryption, is a layeredapproach primarily used on theoutside of unfilled capsules. Theouter layer of a nano-encryptedmarker is overt and can be read witha microscope, while the inner layeris covert and requires a specialreader which contains specificinformation about the product andcompany.

Fighting counterfeitmedicinesSignificant efforts have been seenduring 2013 and 2014 in the fightagainst counterfeit medicines.Counterfeiting and diversion casesmay be rising, but internationalauthorities are improving detectionand prosecution of prescriptiondrug counterfeiters and are workingdiligently to close illegalpharmaceutical manufacturingfacilities and illegal online drugsellers. Countries across the worldare strengthening regulation andcriminal codes aroundcounterfeiting, and privatecompanies are implementinginnovative packaging and trackingmethods that resist forgery. Fakemedicines remain a threat to publichealth, but with internationalcooperation everyone involved inmanufacturing, distributing anddispensing prescription medicationscan help deter these crimes.

About the Partnership forSafe MedicinesThe Partnership for Safe Medicines(PSM) is a coalition of over 70organisations that represents patient



advocates, healthcare professionalsand every part of the supply chainfrom manufacturing to distributionto retail. PSM is committed tokeeping patients safe fromcounterfeits and unsafe medicinesby maintaining the integrity of thedrug supply chain around the world.Keep up with the PSM through ourwebpage, www.safemedicines.org,or via twitter at @SafeMedicines.

References1 Kubic T. Global Trends Situation Report,2013. Presentation at Partnership for SafeMedicines Interchange 2014, WashingtonDC, USA, 18 September 2014.

2 Jack A. Teva Discovers SophisticatedFakes of Popular Drug. The FinancialTimes 2013; April 28.

http://www.ft.com/intl/cms/s/0/bd988804-afed-11e2-8d07-00144feabdc0.html

3 Council of Europe. Counterfeiting ofMedical Products (MEDICRIME).Strasbourg, France: Council of Europe.http://www.coe.int/t/DGHL/StandardSetting/MediCrime/Default_en.asp

4 Partnership for Safe Medicines. Track andTrace Legislation Resource Page. Vienna,VA, USA: Partnership for Safe Medicines.http://www.safemedicines.org/track-and-trace-legislation-resource-page.html

5 Daleiden B. Brazil Finalizes PharmaSerialization and Tracking Regulation.TraceLink Life Sciences Cloud 2013; 18December (blog entry).http://tracelink.com/_blog/no-bullwhip-supply-chain-management-blog/post/brazil-pharmaceutical-serialization-and-tracking-regulation-finalized/

6 Covington & Burling LLP. Description andEvaluation of International PharmaceuticalProduct Serialization and Verification

Systems to Identify Global Best Practices.White Paper. Washington, DC, USA:Covington & Burling LLP; 14 July 2014.

7 Russia Tightens Responsibility for Sale andProduction of Counterfeit Drugs. ThePharmaletter 2014; 30 July.http://www.thepharmaletter.com/article/russia-tightens-responsibility-for-sale-and-production-of-counterfeit-drugs

8 US FDA. FDA Unit Pursues Illegal WebPharmacies. Silver Spring, MD, USA: USFDA; 14 January 2014.http://www.fda.gov/ForConsumers/ucm381534.htm

9 US FDA. What OCI Investigates. SilverSpring, MD, USA: US FDA.http://www.fda.gov/ICECI/CriminalInvestigations/ucm123062.htm

10US FDA. Operations Pangea. SilverSpring, MD, USA: US FDA.http://www.interpol.int/Crime-areas/Pharmaceutical-crime/Operations/Operation-Pangea



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Green analytical chemistryAnalytical chemistry concerns themaximisation of informationobtained from samples in order tosolve problems related to thestructure and composition of thematter. So, it can be considered thateach analytical method is a systemin which the inputs are samples,reagents, previous information,energy and labour consumption andthe outputs are the obtained dataand answers. However, analyticalmethods also generate waste andemissions. In short, such methodsprovide information in order to solveproblems, but also extra costs for anorganisation and risks for bothoperators and the environment1,2.

Green analytical chemistryattempts to avoid, or at leastreduce, the deleterious side effectsof analytical methods by replacing

toxic reagents with innocuous ones;reducing the consumption ofsolvents, reagents and energy; andavoiding toxic waste generation.Therefore, it provides an ethicalagreement with the environmentand workers’ safety and also offersexciting possibilities for thereduction of analytical costs bydecreasing the working scale andcarefully controlling consumption3,4.

Analytical chemistry in thepharmaceutical industryThe pharmacopoeias definerequirements for the qualitative andquantitative composition ofmedicines, the tests to be carriedout on medicines and substances,and the materials used in theirproduction. The objective of thepharmacopoeias is to providecommon standards to control the

quality of medicines and substancesused to manufacture them. Theproduction of pharmaceuticals andthe strict control required is reallyexigent for lot-by-lot production; themain reason for the introduction ofanalytical methods in the qualitycontrol of products is the need toachieve the narrow variation of±10% of the nominal content ofactive principles in formulations.However, the final product analysismust be just a confirmation of thecorrect function of the wholeprocess, and to achieve this, thequality control of raw materials andthe process itself is mandatory toavoid losses and to guarantee thecompetitiveness of the enterprise.

Therefore, raw materials andprocess evaluation, together withthe final product must be analysed.The process analytical technology(PAT) initiative was first proposed bythe US Food and DrugAdministration with the objective ofachieving significant health andeconomic benefits by application ofmodern process control and tests inpharmaceutical manufacturing5. Themain goal of PAT is the design,analysis and control ofmanufacturing through timelymeasurements of critical quality andperformance attributes. It involvesraw and in-process materials andprocesses in order to ensure finalproduct quality. The PAT frameworkcomprises risk management and theuse of at/on-line sensors that help inmonitoring/controlling/designing ofthe processes. In this sense, a varietyof analytical techniques have beenused in the pharmaceutical industry,including Fourier transform infrared(FTIR) spectroscopy6, UVspectroscopy7, near infrared (NIR)spectroscopy8, gas chromatography9

and high performance liquidchromatography10.

Moreover, the accomplishment ofthe legal frame regarding bothworking conditions andenvironmental safety forces theassessment of the quality of indoorand outdoor air and the generationof liquid and solid wastes. Anadditional goal of the analyticalcontrol of wastes can be found intheir valorisation.

As can be seen in Figure 1, it is


GREEN ANALYTICALCHEMISTRY IN THEPHARMACEUTICALINDUSTRYby Sergio Armenta and Miguel de la Guardia*

The importance of greening the analytical methodsemployed in the pharmaceutical industries is

highlighted by suggesting the use of several strategiesbased on: i) direct analysis of samples without anyprevious treatment, ii) miniaturisation, and iii)automation of procedures. Additional advantages ofthose methodologies includes the reduction of theenvironmental impact and operator risks on using theanalytical procedures, always taking into considerationthat the main objective of analytical chemistry is to solvethe problems, but with the lowest possibleenvironmental side effects.

Miguel de la Guardia is full Professor of Analytical Chemistry at Valencia University,Spain. He has published more than 500 research papers and supervised 35 PhD thesis.He has published and edited several books in the fields of green analytical chemistryand food analysis.

Sergio Armenta is a Professor in the Analytical Chemistry Department, University ofValencia. He has authored over 100 peer-reviewed publications. His main research isfocused on green analytical chemistry, and the development of new analytical methodsbased on vibrational spectroscopy and ion mobility spectrometry combined withmultivariate data analysis methods.

clear that pharmaceutical industriesuse several analytical proceduresand it invests in labour, reagents,instrumentation and energyconsumption. Therefore, analyticalactivities in the pharmaceuticalindustry need to be greener in orderto extend their use and to reduceextra costs.

Greening pharmaceuticalanalysisSustainability11–13 is the main termemployed in the literature to avoidthe deleterious side effects ofpharmaceuticals and industrialactivities in this field. It is great thatthe synthesis and development ofnew active principles have had atremendous effect on our lifeexpectations and its quality.However, the input of chemicals intothe environment due to thepharmaceutical industries must bereduced. To do this, advances in thegreening of technical approaches,together with efforts in educationand training, are required in theshort term, keeping in mind thedevelopment of benign compoundswith an easy and fast degradability

after use.The improvement of

pharmaceutical synthesis, togetherwith the use of renewable feedstock,are probably the main strategies forthe benign-by-design sustainablepharmaceutical development.However, we cannot forget theimportance of analytical tasks in themonitoring and control of all steps,and the efforts on greeningpharmaceutical analysis can reducethe environmental impact ofchemicals and contribute to theeducation of people involved inpharmaceutical activities. Forinstance, innovations in processanalytical chemistry and the abilityto obtain and analyse large amountsof data have served as the keydrivers for greening analyticaldeterminations in thepharmaceutical industry5.

Sample treatment is one of themost energy consuming andcontaminating analytical steps. It isclear that one of the best ways forgreening analytical methods wouldbe to avoid the sampling andsample treatment steps, thusreducing, at the same time, the use

of large amounts of organicsolvents, waste generation andenergy consumption. In this sense,spectroscopy provides a usefulexample of a green analyticaltechnique for raw material analysis,process control (temperature in theextrusion step, particle sizedistribution in the milling process,coating thickness, etc.) and endproduct quality.

The miniaturisation of methodsrelated to raw materials, processand end product control offers asimple way to minimise reagents,energy and labour and may onlyaffect the representation ofobtained data. A clear example ofminiaturisation in thepharmaceutical industry is theintroduction of ultra highperformance liquid chromatography.The reduction of particle size andcolumn dimensions allow theimplementation of high throughputapplications where the drasticreduction of the run time with anacceptable resolution of critical pairsis the main goal to be achieved14.

The automation of analyticalmethods and the use of easyportable instrumentation can alsoimprove the analytical informationby reducing the energy andreagents consumed. So, in spite ofthe absence of suitable directmethods that can be employedwithout any sample treatment or byusing totally innocuous reagents,the aforementioned strategy couldbe employed as a preliminaryapproach for greening the mainanalytical tasks (see Figure 2 forsome of the effects of greeninganalytical methods in thepharmaceutical industry).

On the other hand, it must betaken into consideration that thedevelopment of cheap, fast andgreen methods related to activeprinciples will improve their use inaspects regarding the quality of theworking environment and control ofemissions and wastes and it will,surely, open new possibilities for thevalorisation of residues.

Additionally, incorporation intothe methods of on-line wastetreatments will also contribute to

GREEN ANALYTICAL CHEMISTRY IN THE PHARMACEUTICAL INDUSTRY continued

european INDUSTRIAL PHARMACY March 2015 • Issue 24 9

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GREEN ANALYTICAL CHEMISTRY IN THE PHARMACEUTICAL INDUSTRY continued

reduced costs for their externaltreatment, which offers newopportunities for both education ofworkers and reuse of employedchemicals.

Perspectives and futuretrendsAdvances in green pharmaceuticalanalysis will be based on the factthat green methods can be cheaper,safer and more sustainable thantraditional ones. Thus, a renovationof quality control strategies in thepharmaceutical industry can beexpected based on:

i) the extensive use of portableinstrumentation,

ii) direct methods of analysis withoutrequiring sample treatment,

iii) miniaturisation, iv) automation of the used methods,

and v) the incorporation of on-line

decontamination processes forthe in situ treatment of wastesafter the measurements.

However, the most exciting futuretrends in this field will be theextension of the analyticalpossibilities due to the safety andenvironmental nature of themethods and thus the possibility toextend the analytical measurements

employed nowadays to otheraspects, such as those concerningthe quality control of working air, theevaluation of reactor cleaningbetween batches and thevalorisation of residues. This willoffer new opportunities of businessto the enterprises. Additionally, thetremendous advances incomputation and chemometrics willoffer new possibilities for theimprovement of the information tobe obtained from spectroscopymeasurements in order to save time,reagents and costs in multianalytedeterminations.

AcknowledgementsThe authors gratefully acknowledgethe financial support of theMinisterio de Economía yCompetitividad and FEDER (ProjectsCTQ2011-25743 and CTQ2012-38635) and the Conselleria deEducacion of theGeneralitatValenciana (ProjectPrometeo II 2014/077).

References1 de la Guardia M, ArmentaS. Green

Analytical Chemistry: Theory and Practice,Comprehensive Analytical Chemistry,Volume 57. Oxford, UK: Elsevier; 2011.

2 Koel M, Kaljurand M. Green AnalyticalChemistry. London, UK: Royal Society ofChemistry; 2010.

3 de la Guardia M, Garrigues S. Challengesin Green Analytical Chemistry. London,

UK: Royal Society of Chemistry; 2011.4 de la Guardia M, Garrigues S. Handbook

of Green Analytical Chemistry. Chichester,UK: John Wiley & Sons; 2012.

5 Rathore AS, Bhambure R, Ghare V.Process analytical technology (PAT) forbiopharmaceutical products. Anal BioanalChem 2010;398:137–154.

6 Druy MA. Applications for mid-IRspectroscopy in the pharmaceuticalprocess environment. Spectroscopy2004;19:60–63.

7 Liauw MA, Baylor LC, O’Rourke PE. UV-visible spectroscopy for on-line analysis.In: Process Analytical Technology. BakeevKA, Ed. Chichester, UK: John Wiley &Sons; 2010.

8 Blanco M, Bautista M, Alcalà M. APIdetermination by NIR Spectroscopy acrosspharmaceutical production process. AAPSPharmSciTech 2008;9:1130–1135.

9 Sandra P, David F, Szucs R. Someapplications of state-of-the-art capillarygas chromatography in thepharmaceutical industry. Trend Anal Chem2002;21:662–671.

10 Foley DA, Wang J, Maranzano B, et al.Online NMR and HPLC as a reactionmonitoring platform for pharmaceuticalprocess development. Anal Chem2013;85:8928–8932.

11 Special issue on Sustainability. Int Pharm J2010;27(1).

12 Kümmerer K. Sustainable from the verybeginning: rational design of moleculesby life cycle engineering as an importantapproach for green pharmacy and greenchemistry. Green Chem 2007;9:899–907.

13 Kümmerer K, Hempel M. Green andSustainable Pharmacy. Berlin, Germany:Springer-Verlag; 2010.

14Chesnut SM, Salisbury JJ. The role ofUHPLC in pharmaceutical development. JSep Sci 2007;30:1183–1190.

european INDUSTRIAL PHARMACY March 2015 • Issue 2410

Extension to newproblems

Fast

Sustainable

Cheap

Improved information

Less residues

Safety of working conditions

Fast evaluation of new sustainableprocesses

Valorisation of residues

Raw material control

Process control

Quality control of end products

Characteristics

Simplification ofpresent needs

Greeninganalyticalmethods

Figure 2: Effects of greening the analytical methods in the pharmaceutical sector.


Such is the experience of many lifescience companies who seek to“strike it rich” in the lucrative USmarket. It does not have to be thatway. With some advance planning,the right expectations, and adaptionto the local market, the US marketcan be a significant part ofEuropean companies’ sales andprofits.

This article will assume you arestarting from scratch in month 1.The more you can get done beforeyou open your office (or hire abusiness development firm), thefaster you will realise sales revenue.

First quarter, months 1–3Smart companies will begin with awell-developed strategy and a goodunderstanding of the market. Theobjective in the first year is toestablish a base, not necessarily tomake a profit. In fact, mostcompanies would be pleased if theybroke even or even lost a littlemoney as long as they werepositioning themselves for the longterm.

During these first months, youmust answer the following questionsand develop the necessary toolsthat your marketing and salesrepresentatives need to succeed.

1. What products or services areyou going to sell to theAmericans, and do you knowthey will buy them?This seems pretty evident, but acloser look at both the marketand your competition may tellyou a different story. Products orservices that are selling well inEurope may not be received thesame way in the US. In ourexample above, Mr. Wettlerfound that he could not sell hishigh-end machines in the USbecause the American’s have a 3-year obsolescence cycle, actuallyselling older machines andreplacing it with newertechnology. So selling a product“that lasts 20 years” was not wellreceived by the Americans.

2. How are you different from thecompetition? Remember you are competingwith companies from all over theworld, many with more resourcesthan you. You must have a “USP”or Unique Selling Proposition.Often, this is not easy to identify.You need to dig deep and getcreative. Once you have this USPdeveloped, it must be put on allyour sales and marketing

materials. And to reference theexample above. Mr. Wettlerthought his USP was Germanengineering and quality “to last20 years”, not recognising thatthis is not what the Americancustomers want to buy.

One way to be different is tosolve a unique business problemthat your competition has not yetidentified or addressed. If you areselling machinery, thisunidentified problem might behelping your client recycle his oldmachinery. It might be working forhim to keep stock of spare partson his premises. If you are sellingdrugs, it might be a uniquepackaging that speeds fulfillment,or an easy way to order yourproducts. Look for businessproblems, then solve them.

3. What is your marketing planand how much will it cost?The US is larger than all ofEurope and travel is expensive.Trade shows are the best way tomeet new customers, andAmericans are more receptive toworking with new suppliers, soyou need to be visible at theseshows. Shipping trade showmaterials and staff from New Yorkto California to Houston to Miamican be expensive.

You might also base yourmarketing and sales programaround geography. Keep in mindthat it takes one full day of travelto fly from the West coast to theEast coast because it is a 5-hourflight and you lose 3 hours in timezones. You may be able to meetyour sales forecast based only oncompanies in New York, NewJersey, Pennsylvania andConnecticut. All of these statesare in a relatively small area andcan be reached by automobile.One Scottish customer weworked with identified enoughbiotech and pharma companiesin these four states that he savedthousands of dollars and monthsof travel time by concentrating onprospects only in this area.

4. Who are your target accounts? You should have a list of 100prospects identified IN

PLANNING YOUR FIRSTYEAR OF SELLING IN THEUS LIFE SCIENCES MARKETby Jim Worrell

Jurgen Wettler, CEO of a German manufacturer ofpharmaceutical grinding equipment, sat in his office

pouring over the recent sales figures from his USsubsidiary. They were not encouraging. First year saleswere expected to be approximately $2.3 million. Mr.Wettler was looking at sales of just under $900,000.What went wrong?

Jim Worrell ([email protected]) is CEO of AmeriStart, a sales and marketingcompany specialising in the life science industry. He has a degree in InternationalMarketing from Miami University and has held management and marketing positionsin Ghana, the Caribbean, The Netherlands and the US. Jim’s specialty is sales,marketing and distribution strategies in the US and international markets. Hefounded AmeriStart in 2003, which has clients in more than 20 countries.

PLANNING YOUR FIRST YEAR OF SELLING IN THE US LIFE SCIENCES MARKET continued


ADVANCE. This includes thename of the company and thename of the individuals you wantto call on. Don’t show up and tellthe business developmentrepresentatives to “go findcustomers”. Building a targetdatabase takes time and effort,but it can be done. With a “hitlist” in hand, your businessdevelopment representatives willbe much more productive.

5. Americanise your marketingmaterialsImagine a US company selling inyour native country usingbrochures with incorrect German,Italian or French. The nativecustomers would not take themseriously. Hire a good agency andmake sure you have properAmerican English. This goes foryour user manuals and technicalmanuals as well.

6. Think like an American (or hiregood American staff)I recently had the CEO of anIndian company tell me “Ourexecutive team is not usingLinkedIn, because this is not inour culture”. He was overlookingthe fact that LinkedIn is the mostpowerful business tool inAmerica, and not to be there putshis company at a cleardisadvantage.

Quarter 2, months 4–6: beactive, visible and buildrelationshipsThe key to success in the US market(and any global market for thatmatter) is to be active and visible.Do not let your sales representativeshang around the office and justmake phone calls. Get out in themarket and build relationships. Yourbusiness development staff shouldunderstand the problems UScompanies face and developsolutions to solve these problems.

The problems and solutions may bedifferent than those of Europeancustomers, but you will never knowuntil you get out and talk to people.

Go to trade shows, seminars andother industry events. Hire a goodpublic relations firm to get yourname in multiple magazines andwebsites. Write articles, blogs andbe active in social media. Send outmailers and write white papersabout industry issues. Become athought-leader to the 100companies on your target list.

By month 4, 5 or 6, you shouldbegin to see the results of yourefforts and requests for proposalsshould start coming in. Recognisethat while American companies arequick to try new resources, they maystart with small orders to “test thewaters” of a new supplier. Your jobis to ensure that this first orderexceeds their expectations. Dowhatever it takes to make yourcustomer say, “WOW, these guysare good!”

Americans are service-orientedand no matter what industry you arein or what products you sell, you arein the service business. Always keepin mind that, while it’s great to getthe first order, it’s the second orderthat is the most important.

Months 6–12If you have done your job correctlyin the first 6 months, these next 6months are focused on deliveringyour first sales and continuedemphasis on building the business.Follow the steps below.

1. Continue to identify newprospects. Always keep the top ofthe sales funnel full.

2. Refine your marketing positionand message. Based on what youare learning from your first salescalls and first orders, don’t beafraid to “pivot” or change themessage on your website and

marketing materials. You maydiscover a niche that others haveoverlooked.

3. Take care of your first customers.This cannot be overstated.Customers come first!

4. Once you have a customer andhave delivered your first orders,begin to go deeper into theseaccounts. Look for more ways toadd value to these firstcustomers. Look for initiatives intheir companies where yourproduct or service fills a need.Look for additional businessproblems they have based onyour growing relationships withthe clients.

5. Get your senior managementinvolved in these accounts. Onceyour business developmentrepresentatives have opened thedoor and even delivered the firstorder, make it a point to haveyour directors visit these clients.Americans like to know that theirbusiness is important enough towarrant a visit from yourManaging Directors. And often,the Managing Directors will beable to spot opportunities thatthe business developmentrepresentative may not haveseen. Once they spot theseopportunities, he or she has theauthority to take action back inEurope to ensure the companydelivers on these opportunities tomaximise sales to the UScustomer.

As a final thought: be patient. Bewilling to invest for the long term.Take the time to learn the market,adapt your products and yourmarketing message, buildrelationships and solve businessproblems by delivering value. Romewas not built in a day. Neither is theAmerican market.


The first time drug kingpin, TucoSalamanca, tries Walter White’scharacteristically blue meth on theAMC drama Breaking Bad, hispriorities are straightforward: hedoesn’t care about colour, he justwants to get high. “Blue, yellow,pink, whatever man,” he says. “Justkeep bringing me that!”

But as fans of the show alreadyknow, White’s business soonbecomes all about the blue—fromdrug addicts to rival producers,everyone wants White’s signaturetint.

The fictional meth manufacturerisn’t the only one who understandsthe importance of drug colour—onboth sides of the law, it’s a key partof branding. Viagra is famouslyknown as “the little blue pill”,Nexium is marketed as “the purplepill”, and street names for illicitdrugs run through the wholerainbow. But there are also subtlerand arguably more important rolesfor drug colourants. They’re notthere just to make a drug look pretty.

Tuco may have been surprised tolearn, for example, that meth of adifferent colour may have improvedhis high. Studies have shown that weassociate drug colours with specificeffects that stretch far beyond brandrecognition. Once we’ve tricked ourbrains into making the association, itactually becomes real. The placeboeffect comes into play and the drugis more effective.

Imagine burning your skin andtreating the pain with a cream. Isyour imaginary cream white? Nowpicture it red. Would you trust the

cream to work as well? If you had amoment of pause there, you’re notalone. Multiple trials—some withplacebos, others with activedrugs—have shown that patients’colour-effect associations canimpact a drug’s efficacy bymeasuring physical signs like heartrate and blood pressure.Pharmaceutical companies are wellaware of these associations andcarry out extensive related research

when developing new products orrebranding old ones.

Food colour trumps flavourBlue pills, contrary to what BreakingBad may have you believe, act bestas sedatives. Red and orange arestimulants. Cheery yellows make themost effective antidepressants, whilegreen reduces anxiety and whitesoothes pain. Brighter colours andembossed brand names furtherstrengthen these effects—a brightyellow pill with the name on itssurface, for example, may have astronger effect than a dull yellow pillwithout it.

When researchers take culture intoaccount, things get a bit morecomplicated. For instance, thesedative power of blue doesn’t workon Italian men. The scientists whodiscovered this anomaly think it’sdue to ‘gli Azzuri’ (the Blues), Italy’snational soccer team—because theyassociate the colour blue with thedrama of a match, it actually getstheir adrenaline pumping. Andyellow’s connotations change inAfrica, where it is associated with

THE POWER OF DRUGCOLOURby Tessa Fiorini Cohen

Apill's hue can affect how it's judged by patients,how it's marketed, and even how well it works.

Tessa Fiorini Cohen is a pharmaceuticals professional with over 5 years' experience inindustrial research and development. She currently works in quality assurance, with afocus on process validation and minimisation of product cross-contamination risk. Shealso works as a freelance science writer.

THE POWER OF DRUG COLOUR continued


better antimalarial drugs, as eyewhites can turn yellowish when aperson is suffering from the disease.(Interestingly, this is the opposite ofthe norm. Just like with the burned-skin example, drugs usually workbetter when their colour matchesthe intended outcome, not thesymptoms of the condition they’retreating.) Such cultural variances areone reason why a drug may appeartotally different in separatecountries.

Colour also has a more practicalrole in drug manufacturing. In light-sensitive products, tints can lendopacity, keeping active ingredientsstable. Colour, together with shape,also aids drug recognition. Thisensures that drugs aren’t mixed upduring production or packaging—a

scenario that would have terriblerepercussions for patient safety aswell as brand reputation. Andcolour’s role in drug recognition isequally important at the patientlevel, preventing accidentaloverdose by helping patients onmultiple drugs to recognise eachone. This is most relevant to theelderly, who are often on multipledrugs and may be dealing withcomplications from eyesightdegeneration or dementia. It is alsoa bonus to healthcare workers, whohave to give out lots of differentdrugs in a short space of time.Colour’s role here shouldn’t betaken lightly; five percent of allUnited States hospital patientsreceive incorrect medication.

But colour-effect associations can

also backfire—while a drug’s hueacts as a mental imprint, remindingpeople to take their medications,this also means that patients arealso likely to stop their medicationregimen if drug colours arechanged. This is one of the reasonswhy drug manufacturers ferociouslyguard their designs and colours withpatents, and generic companies tryso hard to resemble them.

So no matter what TucoSalamanca may say in a moment ofmeth-induced euphora, the choicebetween blue, yellow or pinkactually matters quite a bit—and it’sanything but random.

©2015, Tessa Fiorini Cohen as firstpublished by The Atlantic

Industrial

Pharmaceutical

Microbiology

Standards & Controls

Editors

Geoff Hanlon

Tim Sandle

2015 edition

Expert Guidance on IndustrialPharmaMicrobiologyEdited by Geoff Hanlon and Tim Sandle

This new second edition is an excellentreference work for those working in industrial

pharmaceutical microbiology. It covers allaspects of this complex subject with

contributions from many leading figures in thefield and is highly recommended

European Journal of Parenteral and

Pharmaceutical Sciences

This book is essential for every pharmaceutical laboratory: scientific, topical and practical.

Pharmig

order online at www.euromedcommunications.comOr contact the publishers: email: [email protected];

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

Industrial Pharmaceutical Microbiology:Standards and Controlsprovides clear, practical and up‐to‐date guidance for handling virtually everycompliance and operational challenge associated with pharmaceuticalmicrobiology.

Expert Advice

In over 600 pages and 25 chapters a team of twenty four internationalauthorities answer all your questions concerning regulatory expectationsin areas such as microbiological audits, rapid microbiological methods,conducting risk assessments, both proactive in terms of minimisingcontamination, and reactive in terms of addressing microbial data deviation;and also ensuring that processes meet “quality by design” principles.

International Applications

Connect instantly with regulations and current best practices on everythingfrom disinfectants to sterility testing; environmental monitoring to hazardanalysis; and from pharmaceutical processes to biological indicators. All ofthis is developed from an international perspective, where differentregulations are compared and contrasted together with insightfulcommentary as to best practices.


This new programme will involve theintegration of the curriculum tosupport the dispersal of practiceplacements throughout the 5 years(rather than concentrated in the finalyear). The three Schools ofPharmacy in the Republic of Ireland(Royal College of Surgeons ofIreland (RCSI), Trinity College Dublin(TCD) and University College Cork(UCC)) have developed newcurricula to facilitate experientiallearning throughout the 5 years ofthe qualification. These changes willenable placement experience ofvarying duration in the three mainpractice settings of community,hospital and industry (shadowplacements in the second year, a4–6-month placement in the fourthyear (industry placement can onlytake place here), and an 8-monthpatient facing placement in the fifth

year). A joint shared services officehosted in one of the schools will beset up to support the placementaspect of the programme.

Considering the extensivepharmaceutical, biopharmaceuticaland medical devices industries inIreland (circa 50K employeddirectly), the number of industry-based pharmacists is low (circa 300).One of the main reasons for suchlow representation was the fact thatthere was only one School ofPharmacy (TCD) graduating a smallnumber of pharmacists for manyyears who were actively recruitedinto community pharmacy by highentry level salaries. This haschanged in recent years with RCSIand UCC now providing pharmacyeducation (170–180 pharmacistsqualify each year). Also, manypharmacists who qualified overseas

now practice in Ireland.The number of current industry

intern placements is small(approximately 20 industry trainingsites approved by PSI). One of themain barriers to increasing thenumber of intern placements hasbeen the legislative requirement(Pharmacy Act 2007) to have an on-site pharmacist tutor supervising thepharmacy intern day-to-day. Many ofthe Irish manufacturing sites do notemploy pharmacists on-site becausethe qualified person does not needto be a pharmacist, as is usual inmost European countries. ThePharmacy Act 2014 allows muchmore flexibility in terms of day-to-day supervision for non-patientfacing placements, and allows foroverseas placements, which willopen up many more internopportunities.

PIER (Pharmacists in IndustryEducation and Regulatory) was setup in 2012 to represent the interestof all Irish pharmacists employedoutside of the traditional patient-facing roles. Since TIP/TIPPSA(previous interest group for Irishindustry pharmacists andpharmaceutical scientists)disbanded, there had been a void interms of a recognisable industrypharmacist group in Ireland forstudents and young pharmacists toengage with. PIER has organised anumber of industry careers eventsover the past couple of years to raiseawareness of the many industry rolesthat a pharmacist can hold. It hasbeen encouraging to see the level ofinterest at these events. Thecommittee is also actively working toincrease the number of summer andintern placements in the short tomedium term. PIER has committedto working with the three schools tohelp them deliver industry aspects ofthe integrated MPharm programmethrough facilitated workshops,shadow placements, site visits andan increased number of internplacements.

For further information on the fullyintegrated MPharm programme,please seehttp://www.thepsi.ie/gns/education/fiveyearintegratedpharmacydegreeprogramme.aspx

IRELAND LAUNCHES ANINTEGRATED 5-YEARPHARMACY EDUCATIONAND TRAININGPROGRAMMEby Maura Kinahan

In recent years, the Pharmaceutical Society of Ireland(PSI) has prioritised pharmacy education reform andcommissioned a root-and-branch review of the 5-yearMPharm programme – the PEARs (Pharmacy Educationand Accreditation Reviews) project (published in 2010).A key recommendation of the PEARs project was theintroduction of a 5-year fully integrated Master’s level ofeducation and training for those seeking to becomepharmacists, replacing the current 4+1 model. Thisrestructuring of the pharmacist qualification willcommence with effect for programme entry inSeptember 2015.

Maura Kinahan is an industry-based pharmacist who has been involved in NationalForum for Pharmacy Education and Accreditation, which advised the PSI on therollout of the integrated MPharm programme, and is still involved in the NationalSteering Committee to support the Schools of Pharmacy in the rollout of theprogramme from September 2015. She is also a PIER committee member leading oneducation and membership.

The IMP is performed incollaboration with IMP partners whooffer the placement. An IMP partnercan be any company or institutionsupporting the EPSA IMP andEuropean pharmacy students byproviding them with vacant place(s)in work or research connected toany field of pharmacy andpharmaceutical sciences.Throughout the years, we havemanaged to collaborate with manydifferent pharmaceutical companies,universities and agencies active inhealthcare policies.

Placements are arranged for aperiod of 3 to 12 months with anappropriate salary to cover basicliving costs in the country where theinternship is performed. Promotionof the placement is advertised overEPSA’s internal communicationnetwork as well as on the EPSAwebsite and social media. Thisensures that not only a high number

of students and recent graduatesare reached, but also promotes thework, the working environment, theimage and the values of the IMPpartner among European pharmacystudents. Based on mandatory andpreferable qualifications for thetrainee set by the IMP partner, EPSApre-selects applicants thus providingto the IMP partner the bestcandidates for the position. The IMPpartner makes the final decision inthe selection process.

One of the EPSA members,Helena Vankatova from the CzechRepublic, shares her experiencesfrom an IMP placement in the EMEA(Europe, Middle East, and Africa)Consumer Healthcare Sales team inthe GlaxoSmithKline (GSK) office inLondon, UK. She started her 12-month internship in February 2014.

“The offered position was withinthe EMEA sales team especially

focusing on expert marketing. Themain reason I applied for the rolewas my passion for pharmacy andlack of expertise in this particularfield. The role description seemedto be a perfect fit to my desire todevelop into a versatile pharmacistwho can contribute to the well-being of patients.

After graduation, I started workingas a pharmacist at the communitypharmacy. Gaining almost 2 years ofexperience in direct contact withpatients helped me strengthen theknowledge learned at university anddevelop into a confident expert.Using this insight significantly spedup the transposition to thepharmaceutical companyenvironment, since many thingsstarted clicking together and myexpert opinion has been valued atall times.

The main responsibilities of theproject involved coordinationbetween individual and team workprojects, maintenance of thepartnership between EPSA andGSK, collaboration with UKpharmacy students, coordination ofvarious market requests forlocalising Expert MarketingeDetailing Sales content, andoverseeing mandatory actionsrequired for the EuropeanFederation of PharmaceuticalIndustries and Associations (EFPIA)Code reporting.”

Additionally, the IMP represents aunique opportunity for students andrecent graduates to gain valuableexperience about foreign Europeancountries, their customs andcultures, as well as to learn and getto know European diversity, whichare the attributes often encouraged


EPSA INDIVIDUALMOBILITY PROJECT – ASTEP INTO APROFESSIONAL CAREERby Svetlana Kolundžić

The European Pharmaceutical Students’ Association(EPSA) Individual Mobility Project (IMP) is a long-

term internship project that gives the opportunity tostudents and recent graduates from all EPSA memberassociations to gain an additional real-time work andresearch experience in any field of pharmaceuticals. It isa unique network developed to offer internationalprofessional experience for students who have strongprofessional and personal ambitions as well as to thosewho are undecided or confused about their professionalfuture path and wish to explore the opportunities in anykind of pharmacy-related professions.

The EPSA represents more than 160,000 students and recent graduates from 36European countries. The Association has a permanent office in Brussels, Belgium andconducts its activities through regular congresses, advocacy activities, training events,publications, exchange programmes and virtual presence. The main aim of EPSA is todevelop the interests and opinions of European pharmacy students and to encouragecontact and cooperation between them. EPSA is actively engaging at student andprofessional level, bringing pharmacy, knowledge and students together andencouraging personal development.

by the European Commission.Helena explains what she gainedout of IMP.

“During the year, I have beenexposed to challenging situationswhich have had a positive impact onpersonal development andexperience gaining. I have evolvedeffective ways of thinking and fastreaction to tasks, efficiency, builtstrong self confidence especially attraining delivery, knowledge transfer,and international meeting speaking.The opportunity to meet colleaguesfrom various markets helped tocreate stronger and trusted businessrelationships.

I would encourage every student

and recent graduate to use theopportunities the IMP are offering.Starting with the applicationprocess, interviews and fulfillment ofthe requirements, this programmetakes individuals out of their comfortzone. Once you are selected, youare going to learn many new thingsin the role, and also get to knowyourself better while beingchallenged by situations you havenever experienced before. From aprofessional point of view, the IMPoffers a unique way to start a careeryou desire.”

IMP partners consider the EPSAIMP as a great source of young,motivated and talented trainees and

are very satisfied with the level ofcommunication, updates andnotifications received from EPSAwhile arranging the trainingplacement. Trainees tend to be ableto work independently, with excellentEnglish communication skills, a highlevel of aptitude in the workingenvironment, and showprofessionalism and knowledge.Because of that, many of our partnerschoose to continue with the IMP anddeepen collaboration with EPSA.

For more information about EPSAand the IMP, visit the EPSA website(www.epsa-online.org) or contact theVice President of Mobility, DomenKutoša ([email protected]).

EPSA INDIVIDUAL MOBILITY PROJECT – A STEP INTO A PROFESSIONAL CAREER continued


PharmacoVigilanceRevıew

Journal on drugsafety issues

Editor – Rob Begnett

This quarterly journal providesinformed comment and analysis ofinternational pharmaceuticalregulations relating to the safe use ofmedicines and medicinal devices. It

also carries reviews of current methods of pharmacovigilance.

Order online at www.euromedcommunications.com

Or email: [email protected]

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


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

USALaunch of Office ofPharmaceutical Quality (OPQ)This new Center for Drug Evaluationand Research office creates a drugquality program as robust as theprograms the agency already has inplace for drug safety and efficacy.The OPQ will streamline the Foodand Drug Administration (FDA)processes that monitor drug qualitythroughout the product lifecycle.

SUPAC: ManufacturingEquipment Addendum This combines and supersedescertain scale-up and post-approvalchanges (SUPAC) guidances. Itremoves the lists of manufacturingequipment that were in affectedguidances and clarifies the types ofprocesses being referenced.

Product Tracing RequirementsCompliance Policy – Guidancefor Industry The FDA recognises that somemanufacturers, wholesaledistributors and repackagers mayneed additional time to work withtrading partners to ensure that allrequired information is provided. Tominimise supply disruptions ofprescription drugs, the FDA doesnot intend to take action againsttrading partners in such cases priorto 1 May 2015.

FDA letter stating thatbioequivalence study protocolscontain safety protectionscomparable to the applicablerisk evaluation and mitigationstrategy (REMS) for thereference listed drug (RLD)This draft guidance describes how aprospective abbreviated new drugapplication (ANDA) applicant mayrequest a letter stating that the FDA

has determined: (1) the applicant’s bioequivalence

study protocol contains safetyprotections comparable to those inthe REMS with elements to assuresafe use applicable to the RLD, and

(2) that the FDA will not consider ita violation of the REMS for the RLDsponsor to provide a sufficientquantity of the RLD to the genericfirm or its agent to allow the testingnecessary to support its ANDA.

Conclusions of the FDA–EMA(European Medicines Agency)parallel assessment of quality-by-design elements ofmarketing applicationsThe US FDA and the EMA arepublishing a series of joint question-and-answer documents that outlinethe conclusions of this first parallelassessment.

“Accidental” administration oftrial materials to patientsThe FDA has become aware thatsome training intravenous productshave been distributed to healthcarefacilities and subsequentlyadministered to patients. There havebeen reports of associated seriousadverse events.

(Readers should note that it isimportant to ensure via the qualitysystem that products which werenever intended for human use, e.g.demonstration/training kits, placebofrom process/machine trials cannotenter the legitimate supply chain insuch a way that they can beadministered to patients. MH)

Europe

Guideline on Setting Health-Based Exposure Limits for Usein Risk Identification in theManufacture of DifferentMedicinal Products in SharedFacilitiesThis final version comes into effecton 1 June 2015 and links in to thenew versions of Chapters 3 and 5 ofthe EU GMP (good manufacturingpractice). The approach is to reviewand evaluate pharmacological andtoxicological data of individual

active substances to enabledetermination of threshold levels asreferred to in the GMP guideline.These levels can be used as a riskidentification tool and also to justifycarry over limits used in cleaningvalidation.

Guideline on Similar BiologicalMedicinal Products This final guideline, effective on 30April 2015, describes and addressesthe application of the biosimilarapproach, the choice of referenceproduct and the principles forestablishing biosimilarity.

Delegated Regulation (EU) No.1252/2014 GMP for ActiveSubstances for MedicinalProducts for Human Use This document provides thenecessary legal framework of GMPprinciples for active pharmaceuticalingredients (Part II of the EU GMPGuide delivers further detail of theseprinciples). The regulation, validsince May 2014, only came into forceon 15 December 2014 and is directlyapplicable in each EU member statewithout a transitional period.

Adaptive pathways: a futureapproach to bring newmedicines to patients?The concept of adaptive pathwaysforesees an early approval of amedicine for a restricted patientpopulation based on small initialclinical studies. The first approval isfollowed by progressive adaptationsof the marketing authorisation toexpand access to the medicine tobroader patient populations basedon data gathered from its use andadditional studies.

Mitigating risks due to the useof antibiotics in animalsThe EMA has publishedrecommendations to limit thedevelopment of antimicrobialresistance linked to the use ofantibiotics in animals. It focuses inparticular on promoting theresponsible use in veterinarymedicine of antibiotics that arecritically important in human


medicine, e.g. fluoroquinolones andthird and fourth generationcephalosporins.

PharmEuropa proposed texts –tabletsThis proposed text requires thattablets with break-marks must befunctional and their efficacyassessed in respect of uniformity ofmass of the subdivided parts.

Medicine and Healthcareproducts Regulatory Agency(MHRA)GMP Data Integrity Definitionsand Guidance for Industry This document provides MHRAguidance on GMP data integrityexpectations. It complementsexisting EU GMP, and should beread in conjunction with nationalmedicines legislation and EU GMP.

MHRA helps pharmaceuticalcompanies develop European(UK) innovative technologysites MHRA advised both ESAI and AstraZeneca on the regulatoryrequirements needed for theinnovative concepts and design

philosophies. One of the processesinvolved includes multiple asepticstages.

(Companies so often design firstand then grumble when the regulatorfinds fault with design – this approachis much more sensible – MH)

Medicines distribution in themaritime sectorFrom 1 December 2014, anycompany continuing to wholesalesuch medicines without a WDA(H)will be liable to enforcement action.

InternationalAustralia & New ZealandCessation of efforts toestablish a joint therapeuticproducts regulator (AustraliaNew Zealand TherapeuticProducts Agency)This decision was taken atGovernment level following acomprehensive review of progressand assessment of the costs andbenefits to each country.

Pharmaceutical InspectionCooperation Scheme (PIC/S)Establishment of PIC/S

Inspectors Academy(PIA)/dedicated facilitiesseminar outcomesPIC/S is to establish the PIA. Thisinitiative to set up a web-basededucational centre aims atharmonising and standardising GMPtraining at an international levelthrough an accredited qualificationsystem.

PIC/S also agreed to establish aPIC/S Expert Circle on DedicatedFacilities, which will draft an AideMemoire on the inspection ofdedicated facilities, and providetraining to inspectors on this difficultissue. As much as 60% of allinspectors have not received anytraining in this critical field: as aresult, the Expert Circle will work oncreating such a training programmefor inspectors.

For further information on these andother topics we suggest you refer tothe websites of relevant regulatorybodies and to current and pasteditions of “GMP Review News”published by EuromedCommunications. To subscribe tothis monthly news service [email protected]

“a real manual – user-friendly, printed and edited in astyle that induces the reader to continual consultation”

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REGULATORY REVIEW continued


Broken“Something about the supply chainis broken,” said the communitypharmacist. “I spend half my timesourcing things.”

“Pharmacists phone me aboutthree times a day saying thatsomething is out of stock,” said themedical general practitioner.“Ordinary things such as genericbenzoyl peroxide. I’m having tosubstitute Edipuo or Duac. It’s afalse economy.”

Something is amiss with medicinesupply in the UK.

The easiest culprit to identify isthe government. Governmentsshould be more aware of the impactupon patients. My hunch is that thehealth professionals attempt toprotect patients from knowingabout problems. But patients realisethat the NHS is strugglingfinancially when crucial scan results,anxiously awaited, are postedsecond class.

Fortunately, there seem to befewer problems with the moreexpensive medicines for seriousdisease.

“I would be very upset if I couldnot get my aromatase inhibitor,”said one patient.

The European Medicines Agencykeeps a list of shortages. Currently,it includes midazolam, imiglucerase,cidofovir, etanercept andmacasermin; all affect comparativelyfew patients.

Governments can lawfully act toreduce the effect of patents if theyadversely affect their citizens’ lives.Specific governments maycompulsorily license medicines.

Indonesia did that for certain anti-HIV medicines; owner companiesmay receive very low royalties (e.g.0.5%).

Maybe the British government ispaying industry too little under theprice regulation scheme. Lessincome means less money forresearch into new medicines.Famously, getting a new entity tomarket is expensive and may take15 years. Lack of reward may evenpose an existential threat topharmaceutical companies. If thepistons of commerce falter,companies may cease to trade.Then, medicine supply ceases andjobs vanish.

StrategiesTo avoid that, industry uses variousstrategies. They may reformulate;that “evergreens” medicines toextend patent life. Post-launch,product prices may be“modulated”. Companies may giveaway products for a time, or heavilydiscount to certain markets. Theirpopulace may be unable to affordonce the subsidy ceases. Thesetactics may keep parallel imports atbay. But if the lower price makes theoriginal product financially moreattractive than the parallel import,more branded original may berequired than can quickly beprovided.

World-wide, there may be onlyone source of an activepharmaceutical ingredient (API); ifthat dries up, immense problemsfollow. Manufacturers must then usean API from a new source. However,progress through current good

manufacturing practice andregulatory hoops may be lengthy.

The US company Gilead Sciencesin 2014 agreed to voluntarily licensecertain anti-hepatitis C anti-virals toseven India-based manufacturerswho would supply to manydeveloping countries, receiving 7%royalties. The alternative may bereceiving nothing as those countriescould not afford non-subsidisedprices. Indeed, a third of the worldcannot afford to access essentialmedicines. I feel guilty about theunfairness of the internationaldistribution of wealth.

I sense you throwing up yourhands at such complexity andsaying, “Not my problem.” But itdoes tar the whole industry. Let usexamine the nature of humankindto see why this is occurring.

Delving deeperThe founding father sociologist MaxWeber remains widely respected.He said that there were only fourreasons for human behaviour. Theyare: selfishness or instrumentality,selflessness or altruism (morality fitshere), tradition: the great flywheelof society, and affectivity: you sobehave because you just like it (e.g.sugaring your coffee because youhave a sweet tooth). I have neverfound a behaviour that they did notcover.

I offer no answer. I expect thatyour industrial “backyard” is inorder. But maybe supply difficultiesdo merit reflection, including byyour movers and shakers.

Malcolm E Brown

bottled brown


PHAR-INFollowing completion of the surveyon competencies in biotechnology,some in-depth, semi-structuredinterviews with managers working inthe biotechnology industry arebeing conducted. Simultaneously,the action plans for undergraduateand a postgraduate series of shortcourses in biotechnology are beingdeveloped.

Healthcare workforceThomas Lion (VAPI/UPIP, Belgium)will represent EIPG at theforthcoming European PharmacyStudents Association (EPSA)reception, which is supported byMembers of European Parliamentfrom Ireland and Romania and to beheld in the International Auditoriumin Brussels.

EPSA/EIPG seminarsThe EPSA and EIPG have recentlyorganised two webinars,internationally accessible asworkshops. The following is a reportfrom Adéla Firlová, EPSA SocialServices and Public HealthCoordinator.

The main topics were thepharmaceutical industry andregulatory affairs with EIPG speakersDr. Georgina Gál (Hungary) and Prof.Claude Farrugia (Malta). The 164participants had an amazing

opportunity to learn from theseindustrial pharmacist professionalsand the opportunity was muchappreciated. Participants weremotivated to join because the topicswere of interest to them andstudents mentioned that they wouldlike to discover job opportunities inthe field of industrial pharmacy.Many would like to work inregulatory affairs.

Anni Svala (EIPG Vice-Presidentfor Education and Careers)introduced the webinars with a shortpresentation on EIPG and this wasfollowed by an introduction onEPSA. Prof. Claude Farrugiapresented on the “Subject(ion) ofPharma” with the latest trendsexplained through graphs andcharts and followed up by answeringa number of questions. Feedbackindicated participants felt the talkwas clear, detailed and interesting.

Dr. Georgina Gál then presentedon a field of pharmacy that is notwell known to many students andcaused some of them to changetheir opinion on the possibility ofworking in Regulatory Affairs. Dr.Gál’s presentation broughtRegulatory Affairs into the spotlightand participants discovered what ittakes to work in this area, how tospecialise and how to reach thedream of becoming a RegulatoryAffairs Manager. Students had manyquestions including the possibility of

internships in Regulatory Affairs andwhat to focus on during pharmacystudies.

Quoting outcomes from studentson the webinars:

“The pharmaceutical industry is avictim of the economic crisis,governments want to pay less fortheir medicines.”“How to follow my dream ofbecoming part of the regulatoryaffairs team.”“EIPG is a very interestingassociation! I am glad there arepharmacists who want to work inand represent pharmacistsemployed in industry.”“Good to learn what the pharmaindustry market looks like.”

After the webinar, 78% ofparticipants who answered thesurvey (72 out of 120) stated thatthey would like to work inRegulatory Affairs, a reallymotivating number! For futurewebinars, participants suggestedtopics such as pharmaceuticalmarketing, pharmacoeconomics andpharmacovigilance.

We hope that the collaborationwith EIPG will continue in the longerterm.

Jane Nicholson, Executive DirectorEIPG, [email protected]

news from the EIPG

CALL FOR ARTICLESDear Colleague

We 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 industrialpharmacy to the journal. All issues of European Industrial Pharmacy are indexed byboth Scopus and Embase and thus are available through the listings for any otherindustrial pharmacist internationally.


eventsMARCH 201519 March 2015 – London, UKCombating CounterfeitMedicines: The Solutionswww.jpag.org

22–25 March 2015 – NationalHarbor, MD, USAPharma Forum 2015 www.cbinet.com

23–24 March 2015 –Amsterdsam, The NetherlandsGlobal BioequivalenceHarmonisation Initiativewww.gbhi.eu

23–25 March 2015 – London, UKPAT and Quality by Design in Pharmawww.patandqbd.com

24–25 March 2015 – Dusseldorf,GermanyPharma Congress 2015www.pharma-kongress.com

25–27 March 2015 – Hamburg,Germany20th Congress of the EAHP: TheHospital Pharmacist’s Agenda –Patient Safety First www.eahp.eu

APRIL 20154–7 April 2015 – Glasgow, Scotland10th Pharmaceutics,Biopharmaceutics andPharmaceutical TechnologyWorld Meetingwww.worldmeeting.org

13–14 April 2015 – Reims, France1st European Conference onPharmaceutics – Drug Deliverywww.apv-mainz.de

14–15 April 2015 – Düsseldorf,GermanyBioProcess InternationalEuropean Summitwww.informa-ls.com

14–15 April 2015 – Berlin, GermanyAseptic Manufacturingwww.pda.org

16 April 2015 – Sandwich, UKAPS Industrial Insights 2015www.apsgb.co.uk

16–17 April 2015 – Munich,Germany Manufacturing of Biologics andBiosimilars http://pharma.flemingeurope.com

22 April 2015 – London, UKThe 14th Joint QP Symposium –QP Responsibilities and thePharmaceutical Supply Chainwww.rpharms.org

22–23 April 2015 – Chicago, IL, USA7th Annual World Drug SafetyCongress Americas 2015www.healthnetworkcommunications.com

24–25 April 2015 – London, UKThe Clinical Pharmacy Congress2015www.pharmacycongress.co.uk

25–27 April 2015 – Lisbon, PortugalConference on the SafetyParadigm for Medicines –Changes and Challenges fromDrug Discovery to Usagewww.eufeps.org

MAY 20154–7 May 2015 – Frankfurt, GermanyISPE Europe Annual Conferencewww.ispe.org

4–7 May 2015 – Athens, Greece2nd Annual InternationalConference on PharmaceuticalScienceswww.atiner.gr/pharmako.htm

5–7 May 2015 – Berlin, GermanyGlobal Pharmaceutical ContractManufacturing Summitwww.gpcmevent.com

5–8 May 2015 – Nice, FranceRDD Europe 2015www.rddonline.com

12–13 May 2015 – Brussels, Belgium5th Annual Life Science ColdChain & Temperature ControlledLogisticshttp://pharma.flemingeurope.com

18–19 May 2015 – London, UK ADC Summit 2015www.smi-online.co.uk/pharmaceuticals/uk/conference/adc-summit

18–20 May 2015 – Berlin, Germany12th Annual BiosimilarsConferencewww.informa-ls.com

19–20 May 2015 – Geneva,SwitzerlandPIC/S–PDA Workshopwww.pda.org

19–21 May 2015 – Brussels, Belgium24th Annual EU PharmaceuticalLaw Forumwww.informa-ls.com

JUNE 20152–3 June 2015 – Amsterdam, TheNetherlandsAdvanced Therapy MedicinalProductshttps://europe.pda.org

9–10 June 2015 – Heidelberg,Germany6th European GMP Conferencewww.gmp-conference.org

10–12 June 2015 – Boston, MA, USA14th Annual World PharmaCongresswww.worldpharmacongress.com

15–17 June 2015 – Geneva,SwitzerlandEUFEPS Annual Meeting 2015 –Systems Approaches for BetterMedicines and Healthwww.eufeps.org

16–17 June 2015 – SwitzerlandPharmaceutical Packaging andLabelling Summitwww.pharmapackaginglabelling.com

23–24 June 2015 – Brussels,BelgiumQuality and RegulationConferencehttps://europe.pda.org

23–24 June 2015 – Brussels,BelgiumPublication & Clinical TrialDisclosure www.cbinet.com

25 June 2015 – London, UKChallenges in Current GMPwww.jpag.org

The aim of the project is threefold: 1. to develop the Delphi

methodology for establishing andevaluating a competenceframework for biotechnologypractice,

2. to propose a framework ofcompetences in biotechnologyfor future and current industrialemployees, and

3. to develop courses necessary forthe acquisition of suchcompetences.

A small expert panel consisting ofthe authors of this paper produceda biotechnology competenceframework by: 1.drawing up an initial list of

competences, and 2. ranking them in importance using

a 3-stage Delphi process.

The framework was next evaluatedby a large expert panel of industrialemployees and academics drawn

from the EAFP, the EIPG, the EFPIAand the European Federation forPharmaceutical Sciences (EUFEPS)5with a snowballing effect forrecruitment of others. Snowballingled to the participation ofpharmacists and others working inareas outside industry andacademia.

Results show that the Delphi tooldeveloped can be used todetermine a consensus frameworkof competences with priorities forcourse development. Thecompetences for biotechnologypractice that received the highestscores were those in:

• Category 1 Research anddevelopment

• Category 6 “Upstream” and“downstream” processing

• Category 7 Productdevelopment and formulation

• Category 8 Aseptic processing• Category 10 Product stability

• Category 11 Regulation.

IntroductionThere is a time gap in knowledgetransfer between industry andeducation. Educational programmesat universities tend to change slowlyand, furthermore, are not always inline with practice. This is in contrastto industry. The latter needs tochange direction and policy withinmonths in order to remaincompetitive. This situation requiresthat the educational system becapable of rapidly offering the rightcourses to produce the right personwith the right competences at theright time. The missing link for sucha development is a system wherebyuniversities can obtain rapidfeedback from industry on what theyshould be teaching.

PHAR-IN has developed a Delphitool for such a feedback processoffering a rapid reaction in a quicklyevolving field leading to thecreation of cutting-edge courses inbiotechnology. This paper presentsthe development of the Delphi tooland the results of the survey on thePHAR-IN framework of competencesfor practice in the biotechnologicalindustry (see Questionnaire for thePHAR-IN survey).

MethodologyDelphi technique Many pharmacy departmentscontinue to use an academicapproach to the development ofcourses that is bereft of sufficientinput from stake-holders and end-users, such as industrial employees.If staff are not actively involved inthe drug industry, they can becomedisconnected from recentdevelopments. Even staff that areactive in industry may be sospecialised as to be unable to graspall the developments. Severalmethods have been developed toovercome this dilemma, one ofwhich is the Delphi process. TheDelphi technique6 (see Figure 1) isan interactive forecasting methodusing a panel of experts that answera questionnaire in several rounds.After each round, a coordinator(s)provides an anonymous summary ofthe experts’ ranking and comments;experts are encouraged to revise


COMPETENCES FORINDUSTRIAL PHARMACYPRACTICE INBIOTECHNOLOGY – THEPHAR-IN PROJECTby the PHAR-IN Consortium

The PHAR-IN Competences for Industrial Pharmacy Practice in Biotechnology1

consortium consists of organisations representing industrial employees, viz theEuropean Industrial Pharmacists’ Group (EIPG)2, the European Federation ofPharmaceutical Industries and Associations (EFPIA)3 and pharmacy academics fromthe European Association of Faculties of Pharmacy (EAFP)4. PHAR-IN is funded by theEuropean Commission via its Education, Audio-visual and Culture Agency; it bears thereference 538252-LLP-1-2013-1-BE-ERASMUS-EKA.

Jeffrey Atkinson, Pharmacolor Consultants Nancy (pcn-consultants), France,[email protected]; Patrick Crowley, Callum Consultancy, USA; KristienDe Paepe, Vrije Universiteit Brussel, Belgium; Brian Gennery, King's College London,UK; Andries Koster, European Association of Faculties of Pharmacy, The Netherlands;Hans Linden, European Federation for Pharmaceutical Sciences, Sweden; ConstantinMircioiu, Universitatea de Medicina si Farmacie “Carol Davila” Bucharest, Romania;Luigi Martini, King's College London, UK; Vivien Moffat, European Federation ofPharmaceutical Industries and Associations, Belgium; Jane Nicholson, EuropeanIndustrial Pharmacists’ Group, France; Gunther Pauwels, Genzyme Flanders, Belgium;Giuseppe Ronsisvalle, Universitá di Catania, Italy; Vitor Sousa, Areta International,Italy; Chris van Schravendijk, Vrije Universiteit Brussel, Belgium; Keith Wilson, AstonUniversity, UK.

http://eipg.eu/wp-content/uploads/2015/03/eip24-pharin-questionnaire.pdf

their earlier answers in light of thereplies of other members of theirpanel.

Delphi methodology has beenused in the biomedical area formany years, for example, for thedetermination of best treatmentoptions7. More recently, thistechnique has been used in the fieldof education to produce consensuscompetence frameworks forhealthcare professionals, such asnurses8 and medical doctors9.

The way in which Delphitechnology was applied in thepresent project is shown in Figure 1.In stages 1 through 3, a small expertpanel consisting of the authors ofthis paper produced a proposal fora competence framework, startingwith an initial Delphi round 1framework produced by BrianGennery and Patrick Crowley. Thethird and final version of thisframework contained 46 proposalsfor competences in 13 categories(see Appendix 1). This proposal for acompetence framework was thenevaluated by a large expert panelconsisting of industrial employeesthat are members of the EIPG, theEFPIA, the EUFEPS and/or otherorganisations, such as the InnovativeMedicines Initiative10, andacademics, members of the EAFP,between 10 July 2014 and 18October 2014.

The large expert panel was invitedvia the internet (usingsurveymonkey11) to rank andcomment upon the 46 proposedcompetences (Appendix 1) using theuni-dimensional Likert method12

with a scale of 1 to 4. Thuscompetences were ranked by givinga score of importance from 1(lowest) through 4 (highest).Members of the expert panels alsohad the possibility to check a “I amunable to rank this premise” box.There was also the possibility ofskipping a competence by notreplying at all (blank). The “unableto rank” and blanks were summed.

The results presented here arethose of the large expert panelconsisting of industrial employeesworking in a biotechnologicalenvironment (n = 82); results are also

given for the total survey population(n = 257) that included, besidesindustrial employees working in abiotechnological environment,industrial employees not working ina biotechnological environment (n =58), persons working in regulatoryaffairs (n = 50), hospital pharmacists(n = 32) and academics (n = 35).

Statistical analysisRanking scores for competenceswere compared using non-parametric methods. The statisticaltests used are described on theGraphPad website13. For descriptivepurposes, results are expressed asmeans. Medians were compared tothe global median using theWilcoxon signed rank test.

Comments were not analysedstatistically.

ResultsSurvey characteristicsParticipants came from all Europeancountries, the main delegationbeing from the UK (16%) followed byPortugal (12%). There were 300entries into the surveymonkeyquestionnaire, of which 43 (14%)were invalid (grossly incompleteand/or duplicates). Of the 257participants, 54% were industrialemployees (n = 140), 32%pharmacists from other areas of theprofession (n = 82) and 14%academics (n = 35). Amongst theindustrial employees and otherprofessions, 25% worked in

regulatory affairs, 22% in researchand development, 8% in production,3% in marketing and 41% in diverseother occupations, such as qualityassurance (31/140 industrialemployees) and hospital pharmacy(32/82 other professions).

Of industrial employees, 36%worked in a small or mediumenterprise, 35% in big pharma and29% in other organisations. A totalof 32% worked in a biotechnologicalenvironment (82/257). Some 76% ofparticipants had a pharmacy degree,20% a science degree and 4% amedical degree. Pharmacists formedthe largest contingency of industrialemployees working in abiotechnological environment (57/82= 69.6%), 23/82 = 28.0% had ascience degree, and 2/82 = 2.4%had a degree in medicine. Severalparticipants stated that they wouldprefer to have a biotechnologycourse in the later stages of theirprimary degree (63%) and 37% asCPD. The bulk of the participants(82%) were aged between 31 and60, the main age category (31%)being 41–50 years old.

Ranking of competences byindustrial employees working in abiotechnological environment (n= 82)The percentages of responsesranged from 76/82 = 96%(competence 1) through 55/82 =67% (competence 19), the globalresponse rate was 2986/3772 = 79%.

THE PHAR-IN PROJECT continued


Figure 1: The Delphi technique as applied in the PHAR-IN project.

1. INITIAL QUESTIONNAIRE

2. EVALUATION BY SMALL

EXPERT PANEL

3. MODIFIED QUESTIONNAIRE

4. EVALUATION BY LARGE

EXPERT PANEL

● production by small expert panel (authors of this article)

● a starting point to be modified in 3 consecutive rounds

● small expert panel: authors of this article

● panel provide (1) rankings, (2) comments (what is unclear,missing, in duplicate, etc.)

● production of modified questionnaire based on rankings andcomments of small expert panel in 3 rounds

● 4th version for evaluation by large expert panel: 46 propositionsfor competences grouped into 13 catergories

● large expert panel: industrialists, academia, pharmacists fromother areas of the profession

● panel provide rankings and comments

The highest percentages of thoseunable to score a competence (“Icannot rank this competence” orblank) were seen in categories 4“Clinical pharmacology” and 12“Ethics and drug safety”. The meansfor competences from industrialemployees working in abiotechnological environment (n =82) are given in Appendix 1.

The highest medians were seen incategory 1 and categories 6 through11 concerned with research anddevelopment, productdevelopment, processing, andstability, respectively. Preclinical andclinical development, biological andadvanced therapy, and ethics anddrug safety scored low.

Ranking of competences by thetotal survey population (n = 257)The global median was 3 and theglobal response rate 8862/11822 =75%. As with ranking ofcompetences by industrialemployees working in abiotechnological environment, thehighest means were forcompetences 1, 25–28, 30, 32, 33and 39.

CommentsThere were 59 comments made outof a possible total of (13 questions x257 participants =) 3,341 (only 1.7%).Comments were made on thefollowing.

1. The clarity of the survey, forexample, regarding preclinicalsciences “your question is notclear enough to provide ananswer”.

2. The context, for example,regarding research anddevelopment “I am not clear inwhat context you are asking theseto be ranked”.

3. The specificity to biotechnology,for example, regarding researchand development “not reallyspecific to biotech products”.

4. The level in terms of foundationor specialist, for example, “I findthe topics listed in each sectionto lack consistency in terms of‘general’ and ‘specialist’

knowledge”.5. The balance between the relative

importance of different areas, forexample, regarding regulatoryaffairs “Fascinating that someonethinks there is more to discuss inregulation than in all other areasof development”.

DiscussionDid the survey technique and theDelphi tool work satisfactory? As 257/300 = 86% successfullycompleted the survey, it appearsthat the survey was comprehensibleon the whole. Of those completingthe survey, response rates were high(all >55%) implying that thosereplying felt well-informed and ableto give a reasoned answer. In somerare cases, response rate was low,e.g. for industrial employeesworking in a biotechnologicalenvironment for categories 4“Clinical pharmacology” and 12“Ethics and drug safety”. This couldbe interpreted as meaning that thegroup had less experience of suchmatters and were less capable ofreplying in these areas.

The Delphi methodology requiresthat the survey be anonymous andso individuals or groups are nottargeted. Thus, no limitations werefixed on the possibility toparticipate, and other professionals,such as persons working inregulatory affairs and hospitalpharmacists, were recruited bysnowballing. It is interesting that theranking profiles of the total surveypopulation were not significantlydifferent from that of the industrialemployees working in abiotechnological environment.Anonymity could be a (minor) issuein this study as Delphi requirescomplete anonymity. In the PHAR-INstudy, the identities of theparticipants were known to theauthors but not to each other.Albeit, one of the main preceptswas maintained, viz that thosesurveyed were not selected. Thisavoids the possibility that the repliesobtained find their origin in thecompetences of the experts chosen.

The number of participants is not

an issue. According to a 2012 surveyby Europabio14, there were 52,540employees in the Europeanbiotechnology industry. Using aconfidence interval of 95% and amargin of error of 10%, the collectedsample size equals 96. The samplesize in this study was close to thisfigure: 82/96 = 85%.

Ranking of competencesHighest scores were attributed to sixcategories:

• Category 1 Research anddevelopment

• Category 6 “Upstream” and“downstream” processing

• Category 7 Productdevelopment and formulation

• Category 8 Aseptic processing• Category 10 Product stability• Category 11 Regulation.

This was true for biotechnologicalindustrial employees and for thetotal population; it suggests thatcompetences associated with thedevelopment and production of theproduct are specific tobiotechnology.

Further papers will deal withother issues such as the statisticalaspects of Delphi/Likertmethodology, whether there is adifference between industrialemployees and academics(educational providers), andbetween industrial employees andhospital pharmacists (users ofbiotechnological products), in whatthey think are essentialcompetences for biotechnologicalpractice.

ConclusionsOn the basis of the scoring and thecomments, the framework nowneeds to be refined in the areas ofthe following.

1. Balance: with development ofsome areas such as formulation,manufacture and quality controland diminution of the importanceof issues non-specific tobiotechnology such as preclinicalpharmacology, reporting of AEs,critical review of published



papers, and safety data in orderto prepare a clinical trial plan.This will be of importance whenproposing a framework for anundergraduate master course.

2. Clarity: with more thought givento possible misinterpretation ofquestions

3. Context: with consideration of thestakeholders of the frameworkand related courses and apossible introduction of a two-tierframework (foundation andspecialist)

If readers of this paper would liketo participate in the PHAR-INproject, they are invited to visit thePHAR-IN webpage:http://www.phar-in.eu/

DisclaimerAs the PHAR-IN project is funded bythe EU, the courses and otherelements are to be produced andused primarily in Europe.

References1 PHAR-IN. Competences for IndustrialPharmacy Practice in Biotechnology(PHAR-IN). http://www.phar-in.eu/

2 European Industrial Pharmacists’ Group(EIPG). Paris, France. http://www.eipg.eu/

3 European Federation of PharmaceuticalIndustries and Associations (EFPIA).Brussels, Belgium. http://www.efpia.eu/

4 European Association of Faculties ofPharmacy (EAFP)http://www.eafponline.eu/

5 European Federation for PharmaceuticalSciences (EUFEPS). Järfälla, Sweden.http://www.eufeps.org/

6 Hsu CC, Sandford BA. The Delphitechnique: making sense of consensus.Practical Assess Res Eval 2007;12.http://pareonline.net/getvn.asp?v=12&n=10

7 Sinha IP, Smyth RL, Williamson PR. Usingthe Delphi technique to determine whichoutcomes to measure in clinical trials:recommendations for the future based ona systematic review of existing studies.PLoS Med 2011;8(1):e1000393.http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000393

8 TUNING Educational Structures in Europe.Competences: nursing practice andclinical decision making. Bilbao, Spain andGroningen, The Netherlands: TheTUNING network.http://www.unideusto.org/tuningeu/competences/specific/nursing.html

9 TUNING Educational Structures in Europe.Competences: medical doctors. Bilbao,Spain and Groningen, The Netherlands:The TUNING network.http://www.unideusto.org/tuningeu/subject-areas/medicine.html

10 Innovative Medicines Initiative (IMI).Brussels, Belgium.http://www.imi.europa.eu/

11 surveymonkey®

https://www.surveymonkey.com/ (ThePHAR-IN survey is given in the annex).

12 Trochim WMK. Research MethodsKnowledge Base. Likert Scaling. NewYork, NY, USA: Research MethodsKnowledge Base.http://www.socialresearchmethods.net/kb/scallik.php

13GraphPad® Software. La Jolla, CA, USA:GraphPad Software Inc.www.graphpad.com/

14Europabio. Brussels, Belgium.http://www.europabio.org/





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european industrial pharmacy issue 24 (march 2015)

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