european Industrial Pharmacy Issue 6 (June 2010)

europeanINDUSTRIALPHARMACY

ISSUE 6 • JUNE 2010www.industrialpharmacy.eu

www.eipg.eu

FEATURES4 THEPHARMINEPARADIGM –MATCHINGTHESUPPLYOF

PHARMACYEDUCATIONANDTRAININGTODEMANDSThe move from big pharma based on chemical synthesis to smallerenterprises based on biotechnology will have a major impact oneducation and training for industrial pharmacists.by Jeffrey Atkinson and Bart Rombaut

8 THE IMPORTANCE OF THE INDUSTRIAL ACADEMICINTERFACE FOR INNOVATION IN THEPHARMACEUTICAL SECTORIndustry and academia need each other. More effort to improvecommunication is needed from the industrial sector, and theacademic sector should be encouraged to find original solutions toserious healthcare problems.by Mike Eaton

12 BIOPHARMACEUTICALS – FROMNICHETOMAINSTREAMA survey of biopharmaceutical companies shows that a largemajority of the independent sector have concerns about mergerswith traditional pharmas, biosimilars and the current patentsystem.by Gareth Williams

15 PERISTALTIC PUMPS – AN ANSWER TO INCREASINGDEMANDS WITHIN THE BIOPHARMA INDUSTRYThese have a number of advantages over standard pumps especiallywhen it comes to cleaning and cleaning validation. There is also norisk of cross-contamination and just a short changeover time.by Henrik Ejsing

18 STABILITY PROGRAMS NEED TO BE RE-INVENTEDCompanies should be aware of the possibility of unexpectedcontaminants – even in secondary packaging material or storagepallets.by Patrick Crowley

REGULARS3 EDITORIAL COMMENT20 REGULATORY REVIEW21 NEWS FROM THE EIPG22 PHARMACEUTICAL FORUM24 JOB VACANCIES26 DATES FOR YOUR DIARY

2 eeuurrooppeeaann IINNDDUUSSTTRRIIAALL PHARMACY • Issue 6 June 2010

europeanIINNDDUUSSTTRRIIAALLPHARMACY

Issue 6 June 2010ISSN 1759-202X

EDITORJoe Ridge, MRPharmS

PRODUCTIONSue Feather

SUBSCRIPTIONSJill Monk

EDITORIAL BOARDMichael AnisfeldMichael Gamlen

Linda HakesJohn JolleyPär Tellner

European Industrial Pharmacy is published three times a year by:

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Belgium: Philippe Van der Hofstadt

Bulgaria: Valentina Belcheva

Czech Republic: Ales Franc

Denmark: Michiel Ringkjøbing Elema

Finland: Tuula Lehtela

France: Jean-Pierre Paccioni

Germany: Armin Hoffmann

Great Britain: Jane Nicholson

Greece: Kiriasis Savvas

Hungary: Sylvia Marton

Ireland: Anna O’Mahony

Italy: Piero Iamartino

Latvia: Inta Saprovska

Malta: Claude Farrugia

Netherlands: Ineke Kleefsman, Michiel Storimans

Portugal: [email protected]

Spain: [email protected]

Sweden: Pär Tellner

Switzerland: Stephan Buchmann; Valter Gianesello

europeanIINNDDUUSSTTRRIIAALLPHARMACYdiscussion group:

www.pharmweb.net/gmp.html

Associate Editors

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

Cover picture: A peristaltic pump head with12 rollers (see p15).

3eeuurrooppeeaann IINNDDUUSSTTRRIIAALL PHARMACY • Issue 6 June 2010

EEDDIITTOORRIIAALL CCOOMMMMEENNTT

continue to play a pivotal role in theEuropean Pharmaceutical Industryand as such we are keen championsof education, professionalcompetencies and in particular therole of the Qualified Person. This yearat the EIPG General Assembly we werepleased to have an industrialpharmacist, Martine Tratsaert fromVAPI/UPIP, our Belgian member, whois also a Board Member of theEuropean QP Association.

Our guests included Roberto Frontiniwho is President of the EuropeanAssociation of Hospital Pharmacists,Bart Rombaut representing theEuropean education initiativePHARMINE and Jurate Svarcaiterepresenting the communitypharmacists of the PharmaceuticalGroup of the European Union.

Also this year, we were pleased towelcome two observers from the Swisspharmaceutical industry, StephanBuchmann, President of GSIA, the SwissSociety of Industrial Pharmacists andValter Gianesello, President of AFTI, theAssociazione Farmaceutici Ticino. DrGiorgio Bruno, Qualified Person forCorden Pharma, Italy, reported on theprofessional development of theQualified Person in the Italianpharmaceutical industry. His overheadscan be found on the website.

I write this Editorial just after theGeneral Assembly of the EIPG whichwas held in Milan and organised bythe Italian Association for IndustrialPharmacy or AssociazioneFarmaceutici Industria (AFI). I wouldpersonally like to thank PieroIamartino, our Italian representative,for his hard work and help inorganising this stimulating and wellreceived event.

I would also like to acknowledge thecontribution of Professor AlessandroRigamonti, the AFI President whosponsored the EIPG General Assemblyand who is also celebrating the 50thbirthday of the AFI as an organisationdedicated to the PharmaceuticalIndustry. I have to say after readingthe programme of the AFIsymposium in Rimini, the AFI seemsa very healthy Association with stronglinks to Academia and is an exampleof best practice for us all.

The discussion points and outcomesof the General Assembly have beensummarised and are to be found onpage 21 of the Journal. As the skillsets needed for staff in today’sPharmaceutical Industry arechanging, so the career pathways forindustrial pharmacists are evolving.Pharmacy remains as a mostversatile qualification. However,whilst the industry consolidates andoutsources into global markets,European pharmacists need thesupport of strong professionalbodies.

The mantra of EIPG is always focussedon ensuring that pharmacists

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The education competencies neededby a pharmacist on Day 1 ofgraduation were agreed and arelisted on our website. It wasconcluded that a general AdvancedMasters in industrial pharmacy is notrequired by most of our members.However, specific diplomas orMasters courses in specialist subjectssuch as clinical trials management,regulatory affairs or quality assuranceare needed for a successful career inthe Pharmaceutical Industry. ProfPaola Minghetti, University of Milanjoined the education working groupand the overheads that she preparedfor the meeting on the Italianeducation system can be found onthe PHARMINE website,www.pharmine.org/pharmine.

As always, the EIPG Bureau andCommittee are open to feedback,suggestions, areas for concern andany matters relating to EducationalPolicy and Standards. Any individualmember can obtain a copy of thefull minutes from me or from yourcountry representative.

To contribute to the Journal or tocontact the Bureau please use ourwebsite www.eipg.eu and contactthe Bureau members direct.

With best wishes

Jane Nicholson,

Executive Director EIPG


JEFFREY ATKINSON, EmeritusProfessor Nancy University,Executive Director ofPharmacolor ConsultantsNancy (PCN), 12 rue deVersigny, Villers, [email protected]

BART ROMBAUT, Professor,Department of Microbiologyand Hygiene, School of Pharmacy, Vrije Universiteit Brussel,Brussels, [email protected]

� “The balance between theoretical andpractical training shall, in respect ofeach subject, give sufficientimportance to theory to maintain theuniversity character of the training.”

The above factors impact mainly onduration and organisation of educationand traineeship. In essence, they statethat a pharmacy diploma should be givenafter a 5-year fully integrated course thatincorporates a 6-month traineeship.

Directive 2005/36/EC also gives someindication of the subject areas to betaught: “Annex V.6. PHARMACIST 5.6.1.Course of training for pharmacists: Plantand animal biology/Physics/General andinorganic chemistry/Organic chemistry/Analytical chemistry/Pharmaceuticalchemistry, including analysis of medicinalproducts/General and appliedbiochemistry (medical)/Anatomy andphysiology; medical terminology/Microbiology/Pharmacology andpharmacotherapy/Pharmaceuticaltechnology/Toxicology/Pharmacognosy/Legislation and, where appropriate,professional ethics.”

Movement of pharmacistswithin EU

This directive is primarily concerned withthe free movement of pharmacists withinthe EU. At the present time this probablydoes not involve a large number ofpharmacists. For example, a surveypublished in 2009 by the French Councilof Pharmacists found that there were 926foreign pharmacists working incommunity pharmacy practice in France– out of a total of 55,523. Of the 926, 181came from the EU, Monaco orSwitzerland2. This may change in thefuture. The survey by the French Council

The first two demands on pharmacyeducation and training will have animpact mainly on duration andorganisation of education andtraineeship.

The first demand concerns the EUdirective 2005/36/EC on the recognition ofprofessional qualifications1. The abolitionof obstacles to the free movement ofpersons and services is one of theobjectives of the EU. For nationals of themember states, this includes their right topursue a profession in a member stateother than the one in which they haveobtained their professional qualifications.Access in the member states to theprofession of pharmacist is conditionalupon the possession of a givenqualification ensuring that the personconcerned has undergone training whichmeets the minimum conditions laiddown. The main factors involved are:

� “Evidence of formal qualifications as apharmacist shall attest to training of atleast five years' duration,…”

� “…four years of full-time theoreticaland practical training at a university orat a higher institute of a levelrecognised as equivalent, or under thesupervision of a university;”

� “…six-month traineeship in apharmacy which is open to the publicor in a hospital, under the supervisionof that hospital's pharmaceuticaldepartment.”

THE PHARMINEPARADIGM – MATCHING THE SUPPLY OFPHARMACY EDUCATION ANDTRAINING TO DEMANDS

by Jeffrey Atkinson and Bart Rombaut

The roles and responsibilities of the modern-daypharmacist are evolving very quickly, and pharmacy

education and training will have to adapt in order toprovide the competences needed for the new roles andresponsibilities (see Figure).

PHARMINE(Pharmacy Education inEurope)

The Pharmine project will examine theopportunities for the introduction of theBologna declaration into pharmacyeducation and training with ethe aim oftuning the latter to the future needs in thethree areas of pharmaceutical expertise:community, hospital and industry pharmacy.


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of Pharmacists reported that “10countries (Belgium, Denmark,France, Iceland, Netherlands,Poland, Rumania, Slovakia, Slovenia,Switzerland) told us they alreadyhave a shortage of pharmacists, and5 (Denmark, France, Latvia, Slovakia,Slovenia) today believe such will bethe case 10 years from now.”Furthermore, if one judges from theEU ERAMUS scheme3, the (student)population of some countries showsmore inclination to mobility thanothers. Comparing the 4 countries(Belgium, France, Italy, Netherlands)that founded the EU (together withLuxembourg not included asnumbers are very small) in 1952,with the 8 countries (CzechRepublic, Estonia, Hungary, Latvia,Lithuania, Poland, Slovakia,Slovenia) that joined (together withMalta not included as numbers arevery small), the EU in 2004, the ratioof students going abroad to that ofstudents coming in from elsewhereis 1.0 (range 0.7 through 1.2) for theold members and 2.2 (range 1.2through 3.4) for the new members.Whilst more mobile pharmacystudents do not necessarily turn intomore mobile pharmacists, thedifference in the numbers is striking.

The Bologna declaration

The second demand on pharmacyeducation and training is the Bolognadeclaration. It should be noted at theoutset that the Bologna declaration isa collection of principles agreed uponby several European countries but –unlike directive 2005/36/EC – it is notEU law and thus not legally bindingin the EU.

The purpose of the Bologna accordsis to create a framework for theconstruction of the European highereducation area (EHEA) by makingdegree and quality assurancestandards comparable andcompatible throughout Europe. Itwas signed in Bologna in 1999 bythe ministers of education from 29European countries4. The Bolognadeclaration concerns all university

Figure. The PHARMINE paradigm – matching pharmacy education and training todemands.

EHEA: European Higher Education Area; B/M/D: bachelor/master/doctorate; LLL: lifelong learning; CPD: continuing professional development

degrees not only pharmacy. Albeit itcould have a varying impact onpharmacy education.

Some principles such as "Adoptionof a system of easily readable andcomparable degrees” (implying thatcountries should adopt commonterminology and standards) arerelatively neutral in their impact.

Other principles such as theadoption of an ECTS (EuropeanCredit Transfer System) system of

credits with links to LLL (lifelonglearning) could have a positiveimpact on, for instance, the linksbetween pre- and post-registrationtraining.

Other principles are moreproblematic: "Adoption of a systemessentially based on two maincycles, undergraduate and graduate.Access to the second cycle shallrequire successful completion offirst cycle studies, lasting aminimum of three years. The

EU directive2005/36 onmutualrecognitionin sectoralprofessions

Bolognadeclarationon EHEA–B/M/Dsystem

Evolution ofeconomic &orgnisationof nationalhealthcare

Evolution ofeconomics,strategy &organisationof industry

Duration ofstudies

Preregistration pharmacy education and training

Traineeship Subject areas

Present andfuture needsin communitypharmacy

Present andfuture needsin hospitalpharmacy

Present andfuture needsin industrialpharmacy

Generic vsspecific

Post-registrationLLL/CPD

DEMAND

SUPPLY

degree awarded after the first cycleshall also be relevant to theEuropean labour market as anappropriate level of qualification."

Thus the Bologna principles divideuniversity education intoundergraduate (bachelor, 3 years)and postgraduate (master, 2 years. Ata later stage doctorate, 3 years’duration was brought in). One of theobjectives of the PHARMINEconsortium is to evaluate whetherand/or how this is relevant to thelong (5 years) integrated course ofpharmacy education and training, orwhether there has to be an exceptionin the case of training for sectoralprofessions such as pharmacy.

The Bologna principles will have animpact mainly on the organisationof pharmacy courses. The two finaldemands on pharmacy educationand training to be considered willhave an impact mainly on thesubject areas taught and theequilibrium between generic andspecific subjects and skills.

Community and hospitalpharmacists

The third demand on pharmacyeducation and training stems fromthe fact that several Europeancountries are reflecting upon waysto develop the services offered bycommunity and hospitalpharmacies in order to strengthenthe roles and responsibilities ofcommunity and hospital pharmacistsin the national healthcare system.Such developments will inevitablyhave an impact on pharmacyeducation and training.

Some of the areas in whichcommunity and hospitalpharmacists may play a greater rolein a given national healthcaresystem5,6 include:

� Provision of new pharmaceuticalservices in risk management,testing and/or management ofchronic health problems such as:smoking, heart disease,

hypertension, diabetes, obesity,chronic renal disease, asthma…

� Evaluation of and reporting onmedicines and medical devices inareas such as: clinical research,pharmacovigilance, efficacy andadverse effects of medicaldevices…

� Evaluation of and reporting onissues of public health such asdevelopment of resistance toanti-microbial drugs…

� Advice to special groups such as:international travellers(vaccinations, diseaseprevention), young mothers (babyfoods), athletes (nutrition)…

� Establishment of evidence-basedmedicines and therapy

� Development and running ofsystems of telemedicine

� Provision of basic first aid

� Interaction between communitypharmacies and residential carehomes

The ways in which the abovechanges in pharmacy practice mayimpact on pharmacy education andtraining include:

� Introduction of new subject areassuch as pharmaceutical care. Thelatter can be defined as theresponsible provision of therapyfor the purpose of achievingdefinite outcomes that improve apatient's quality of life: cure of adisease, elimination ofsymptomatology, slowing of adisease process, prevention of adisease or symptomatology. Itimplies direct involvement of thepharmacist in the healthcareteam responsible for the design,implementation, and monitoringof a therapeutic plan.

� A change in the importance ofgeneric subjects and skills such asmanagement and informationtechnology, and in that of certainspecific subjects such as statisticsand experimental design,gerontology...


� Reflection on the possibleintroduction of a period (e.g. 1styear) of common studies withstudents in other healthcareprofessions (medicine, nursing…)in order to create ties betweenthe different members of thehealthcare system.

Hospital pharmacists are part of themedication management team inhospitals that is responsible for howmedicines are selected, procured,delivered, prescribed, administeredin order to optimise thecontribution that medicines canmake to producing desiredoutcomes. Albeit, the specific rolesand responsibilities of hospital asopposed to community pharmacistsneed clarification in some countries.Once this is done pharmacyeducation and training will againhave to adapt to the new situation.

As national healthcare systems differin the EU, the ways in which the rolesand responsibilities of communityand hospital pharmacists areelaborated and defined will differaccording to local conditions. So tosome extent will the education andtraining judged necessary to obtainthe competences required for suchroles and responsibilities.

The pharmaceuticalindustry

The fourth demand on pharmacyeducation and training stems fromthe rapid changes in thepharmaceutical industry7,8. Changeis dictated by several developments:

� As the population ages newmedical needs emerge andgenerate a different diseaseburden (e.g. the growing need fortreatment of neurodegenerativediseases like Alzheimer’s). The so-called “grey factor” will alsoglobally boost the need for newmedicines as the elderly areoften under poly-medication.

� As the E7 countries (Brazil, China,India, Indonesia, Mexico, Russiaand Turkey) develop


economically, their diseaseburden changes (e.g. emergenceof chronic cardiovascularconditions such as heart diseaseand hypertension) and thus so dotheir medical needs. Theirincrease in wealth also meansthat they play an increasinglyimportant role in pharmaceuticalmarketing and economics.

� Global warning will have a majorimpact on disease patterns. Itmay bring previously eradicateddiseases such as malaria andcholera back to countries inSouthern Europe. It could boostthe production of pollen and soaggravate respiratory illnesses.Small rises in temperature willmodify bacterial growth andhence change microbial diseasepatterns. The examples arenumerous.

In the face of these and otherchallenges, the pharmaceuticalindustry suffers from a lack ofproductivity in the lab. Costs in R&Dsoar but fewer and fewer innovativemedicines are produced.

Furthermore, healthcare agendaand politics – no longer scientificadvancement – have a majorimpact on the development ofpharmaceuticals.

All the above factors are modellingthe face of the industry as it movesaway from the “old” system of bigpharma with innovation andproduction based on chemicalsynthesis, towards one of small andmedium enterprises (contractresearch organisations and thelikewise that are often developed byuniversities), with innovation andproduction based on biotechnology.

This will impact upon educationand training for industrialpharmacists. Changes will berequired in the generic subjects andskills behind the competences infields such as management. Newfields of expertise are emerging suchas legislation on intellectualproperty – the latter being of primeimportance in variousbiotechnological fields such as celltherapy, and allo- or xeno-transplantation. This could produce“double competence” studyprogrammes such as pharmacy plusbusiness management or pharmacyplus patent law.

There will also be a need for achange in subject areas. Here thestrategy to be adopted is very hardto discern. Although the elucidationof the human genome revealedmany opportunities for the industry(e.g. over 800 new drug targets inthe form of G-protein coupledreceptors), and the “–omics” thrivedin higher education institutions andelsewhere, this did not produce thepharmaceutical revolution hopedfor. With hindsight, perhaps toomuch time was spent in faculties onstudies in genetics and genomics -before reality hit home. If in thefuture, education and training is toproduce the right industrialpharmacist specialist at the righttime, given the long-term nature ofdrug R&D, changes in curricula haveto be made a decade before theirfruits can be seen.

The PHARMINE consortium9 islooking at how the pharmacyeducation and training supplied byEuropean universities meets theabove demands and how it will


have to be modified in order tomeet the challenging, futuredemands.

References

1. DIRECTIVE 2005/36/EC OF THE EUROPEANPARLIAMENT AND OF THE COUNCIL of 7September 2005 on the recognition ofprofessional qualifications. Available et :http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:255:0022:014:EN:PDF

2. European survey of employed pharmacistsworking in community pharmacies andtheir mobility. Parésys-Barbier, J., et al. forthe French Council of Pharmacists, 2009.Available at: http://www.ordre.pharmacien.fr/upload/Syntheses/283.pdf

3. ERASMUS mobility data (2007, 2009) from:http://ec.europa.eu/education/programmes/llp/erasmus/stat-en.html andhttp://epp.eurostat.ec.eurpoa.eu/ See alsoEACEA/Eurydice “Higher Education inEurope: Developments in the BolognaProcess”, March 2009. Available at:www.eurydice.org

4. The Bologna Declaration on the Europeanspace for higher education: an explanation.Available at: http://ec.europa.eu/education/policies/educ/bologna/bologna.pdf

5. Pharmacy in England, Building on strengths– delivering the future. Her Majesty’sStationery Office, 2008. Available at:www.official-documents.gov.uk/

6. Le pharmacien d’officine dans le parcoursde soins. Rioli, M. et le groupe de travail,2009. Available at: www.uspo.fr/

7. Pharma 2020: The vision. Which path willyou take? Price Waterhouse Coopers, 2007.Available at www.pwc.fr

8. The continuing evolution of thepharmaceutical industry: career challengesand opportunities, Steiner, M. et al., RegentAtlantic, 2007. Available at:www.regent.atlantic.com

9. The PHARMINE consortium: Coordinator:Bart Rombaut, School of Pharmacy, VrijeUniversiteit Brussel, Brussels, [email protected]

With the support of the LifelongLearning Programme of theEuropean Union (142078-LLP-1-2008-BE-ERASMUS-ECDSP).www.pharmine.org


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THE IMPORTANCE OFTHE INDUSTRIALACADEMIC INTERFACEFOR INNOVATION INTHE PHARMACEUTICALSECTORby Mike Eaton

The pharmaceutical sector has, in recent years, sufferedfrom a perceived lack of successful new drugs, especially

blockbusters. There is much debate as to the causes of this,but the current regulatory and financial environmentrequires that the sector tackles new and innovativetherapeutic targets that challenge its current science base.These new targets will continue the shift away from chemicalentities (NCEs), to biologicals and in the longer term toexplore all “drug space”. “Drug space” that is not part of thecurrent pharma repertoire includes higher molecular weightdrugs eg. nanomedicines, nucleic acid-based drugs1, and“non-Lipinski” inhibitors of protein-protein interactions(Figure 1). As a result the therapeutic sector is activelylooking outside its walls, taking lessons from the biotechrevolution, for new thinking from academics and SMEs.

companies are currently trying to avoididea stagnation by encouraging clusters ofstart-ups businesses – research incubatorswhere less conventional ideas can beevaluated, or through creating smaller,devolved research groups with greaterindependence and autonomy.

The whole pharma sector is beingsqueezed by generic companies, whosesales are predicted to have ~90% of theglobal market which was $820bn in 2009.Many companies no longer find “me toos”commercially viable and as a result arefocusing on difficult drug targets withhigh unmet medical need, outside thetraditional pharma comfort zone. Withinthe non-generic market, biologicals andantibodies are competing with NCEs formarket share with the expectation thatwithin ten years they will share therevenues equally2. We are now seeing theemergence of new therapeutics,occupying the last remaining untouchedtheoretical drug space (Figure 2).

Drug space can be defined by molecularsize going from aspirin (picometre) tostem cells and regenerative medicine(micrometre or larger). Early examples oflarger drugs are nanoparticulates butnucleic acid-based therapeutics andregenerative medicine are just around thecorner. In parallel, there are steps tobroaden the market for the major drugclasses, such as NCEs inhibiting protein-protein interactions and antibodies thattackle intra-cellular targets, currently theexclusive providence of NCEs.

Therapeutics are set to become muchmore eclectic with the emergence ofthese new modalities. These are difficultchallenges and the pharma and SMEsector is once again looking forinspiration from academia. It hashappened before – not so long ago – andgave rise to the biotech sector. Canhistory repeat itself?

The communications dilemma

A problem for both academia andindustry is the lack of a commonunderstanding of the technical issuesfacing drug discovery in the 21st century.Does academia, especially in Europe,have an understanding of what isrequired in the present pharmaenvironment?

MIKE EATON is head ofantibody chemistry at UCB,Slough, UKemail:[email protected]

Examples from the past

Historically, industrial-academic contactin the NCE area has been, in general,limited to the education of newemployees. This interface changedsomewhat with the emergence of thebiotech industry, largely based on thenew and unexpected molecular and cellbiology tools developed by the academicsector, especially in the US.

These opportunities were seized byvisionary entrepreneurs and despite theconservatism and scepticism of largecompanies, new businesses, such asGenentech and Amgen were formed andwere successful. Large companies can beslow to take on transforming technologies,having evolved processes which supportincremental technical improvements, witha view that they can later buy in additionalrequired technologies. Some enterprising

The sides have drifted apart,perhaps due to industrial arrogance,but there is also a perception thatacademic freedom may be adverselyimpacted by working on industrialapplied research. Certainly “BlueSky” research should be encouraged– national research councils andespecially the peer review systemprobably do not do enough tosupport this type of activity.However there is within Europe aconsiderable body of fundedresearch that purports to betherapeutic and hence is appliedresearch by definition. Appliedresearch, academic freedom and“Blue Sky” are totally compatibleand these seemingly different andantagonistic approaches can andmust be brought together toproduce radical high value newproducts.

How is this publicly-funded appliedresearch strategically guided? Ingeneral it is down to the individualand the reviewer to judge whetherthe project objective fits into anindustrial wish list. EuropeanTechnology Platforms (ETP) havebeen brought into being by the ECto advise, from an industrialperspective, how tax payers’research monies should be bestspent.

The Commission’s objective in thetherapeutics sector is both to fundacademic research into newtreatments and diagnostics fordiseases and to support Europeanpharmaceutical industries efforts tobe more competitive.

The author’s experience with theETP on nanomedicine3 has shownthat there is a significant need for

more information flow fromindustry to academia. Without thisinformation, much of Europe’sfunded research will be non-translatable to industry, the clinicand ultimately the patient;consequently much needed newideas will not reach the pharmasector.

The value of communication

Whilst academics are familiar withtheir departments being given a starrating by peer review, most will beunaware that industry often reviewdepartments and individualsindependently. Industry will notonly choose to work with the bestscientists but also those mostinformed on what is needed totranslate an idea to a product.

Breakthrough research requires aless conservative mentality on thepart of grant reviewers.Traditionally, chemistry reviewershave strongly favouredextrapolations from the publishedliterature. Equally it requiresinformed investigations to recognisewhere discoveries or serendipity canproduce step changes for scienceand industry.

So we need to:

� Select fertile research areas (forindustry)

� Explore good ideas or hypotheses

� Leave room for serendipity andmost importantly its recognition

� Create more academic-based keyopinion leaders with industrialknowledge.

What’s in it for industry?

Providing information for academicscientists is a time-consumingactivity that conflicts with mountingpressures on many BusinessDevelopment departments and theirindustrial R&D colleagues.Academics need to know whethertheir idea is applicable, itsmanufacturability and why it has

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Drug delivery systems

Nanomedicines

Vaccines

Biologicals

Antibodies

NCEs

Figure 2. New molecules entities approved in 2008 by Class.

NCEsBiologicals

NCEs

NCEsBiologicals“Non Lipinski” NCEsNanomedicines

Regenerative MedicineNucleic Acids

Figure 1. Diversification of “Drug Space” after the Biotech Revolution.


not been done before. They need tounderstand the industrialrequirements and their project’spotential position in the industrialR&D process. Regrettably, much ofthis experience has not beenpublished, neither is it academicallyaccessible, and the commercialframework is changing all the time.

Fortunately the traditional secrecybarriers are slowly being pulleddown, as the need to search globallyfor ideas takes root in forwardlooking companies. For academiathe benefits are fiscal, highly-ratedpublications, being in the drivingseat for new industrial sectors andthe identification of new healthcareareas which can help patients.

What’s in it for academics?

Whilst some individuals areperfectly happy to just publish theirresearch, some departments areincreasingly trying to build bridgeswith industry. Their aim is toincrease potential funding – butalso to solve real healthcareproblems. There are perhaps twoapproaches to applied research:

� Laissez faire (default strategy)

� A more informed (but notmanaged) strategy

Given that academics by and largeare not familiar with the patentliterature or current industrialpriorities the former approach issomewhat wasteful albeit it couldproduce a “Black Swan”4, aserendipitous discovery that wouldproduce a paradigm shift. Industrialexperience is not well documented,but knowledge of it could reducetime spent on research with nopossible commercial translatability.It is important that commercialinformation and experience isavailable to academics, but that noattempt should be made to imposeindustrial management processes. Itis better to know and understandthe perceived industrial roadblocksfrom the outset, rather than totravel hopefully.

The known obstacles tothe market

Very often translatability ofacademic research is predictablefrom the outset, or if the route isnot so clear then at least theroadblocks can be identified andstrategies developed to overcome orbypass them. The author has comeacross many such predictable andmanageable roadblocks, thefollowing are purely illustrative!

Drug pharmacokinetics

The importance of in vivo DMPKstudies is often not appreciated byacademics, especially those ofinorganic materials that have notcommonly been into man, forexample silica and gold particulates.Very significant work has been doneon gold imaging and therapy, butunless there are appropriateclearance studies these will remain inacademic laboratories and will not betranslated to the clinic.

Another area requiring much more invivo work is polymer therapeutics;polymer clearance being very difficultto monitor in vivo or in urine orfaeces. Synthetic gene therapy vectorshave also stagnated because of areluctance to carry out in vivo studies.

Drug stability

In the drug delivery field mucheffort has been expended on drugrelease systems exploiting thelysosome’s lower pH, followingendocytosis of a delivery system.Such systems often use a stabilisedSchiff’s base, consequently they areinherently unstable to low pH.

To produce a marketed product fromsuch a conjugate requires a simplereliable process and low exposure towater even at pH 7, to ensure thatbatches are analytically reproducibleto regulatory requirements. The fieldof antibody drug conjugates haswrestled with this problem for adecade and has now adopted amanufacturable stable linkage

approach – this industrial lesson hasnot transferred into related academicresearch, often with disastrous resultson scale-up.

Polymer therapeutics

The use of polymers in therapeutics ispart of a multi-billion dollar sector.Aggregation of some polymers couldlead to anaphylactic shock orimmune responses, but polymer self-association studies are often left untilthe pre-clinical stage. As althoughnature has evolved natural polymersnot to aggregate at lowconcentrations, commercial productsare formulated at highconcentrations.

Industrial context

Often the answer as to why aconcept has not been implementedbefore is there is no appreciation ofwhat the advantages must be. Anexample here is molecularimprinting of polymers to atherapeutic target. This technologyrequires a substrate at a one-to-oneratio to imprint an expensivepolymer. Such systems oftencompete with antibodies, whichhave much higher affinities and arecheaper and easier to scale up.Understanding the industrialcontext of your research isimportant if you are to make themost of your efforts.

Cost

DNA cages are an interesting way toentrap a drug, which potentiallycould be released by a particularmRNA relevant to a specific disease.Nucleic acids are, however, veryexpensive drug delivery materialswhen accessed by chemicalsynthesis. It is likely that the futureof nucleic acid therapeutics lies inother directions where they are theagent rather than the formulant ordrug delivery system.

Analytical challenges

The new types of drugs being



discussed throw up many analyticalchallenges. Analytical chemistry isoften regarded as routine but withthe advent of such diverse drugtypes it is a challenge for GMP andin vivo studies. It may even be asignificant obstacle to progressing todevelopment; a point that is oftennot appreciated by those notdirectly involved.

What can we do to improveindustrial-academiccommunication?

This is a challenge which has noeasy solution but it must involvemore effort from the industrialsector. The following are ideas buteach researcher or departmentshould have a local strategy.

� Better industrial peer review ofapplied research proposals

� More effective industrial contactswith universities

� More industrialists connectedwith major research departments

� More sabbaticals in industry andvice versa

� A change in academic culturewhich encourages and rewardsreal innovation andentrepreneurship in Europe

� Each academic departmentdeveloping an industrial liaisonpolicy

� An available source ofinformation on industrialpriorities

� Industry should share itsspecialised technologies andexpertise

� Create “reverse symposia” onwhat industry needs or what theydo not know.

Summary

For the pharmaceutical sector tosurvive in Europe it needs thesupport of academia. There is aneed for more industrial experienceto be available to the academicsector which should be encouraged

to find original solutions to serioushealthcare problems.

Equally, for academia to flourish inEurope it needs the continuation ofits science-based industries and adialogue with industry.

Another question which needsanswering is whether the US isbetter than Europe in producingtranslatable research? Perhaps thestreak of entrepreneurship is not soevident in European culture, forcultural or fiscal reasons. This aspectwill not be changed by spending yetmore money on research, and itvaries quite considerably betweenEuropean countries. R&D is now aglobal activity within the industrialsector – no longer restricted to itsnational or continental boundaries.

References

1. www.archemix.com/website/_popup_press_release.php?release=54

2. Witty, A. Scrip 2008.3. www.etp-nanomedicine.eu/public4. The Black Swan, Nassim N Taleb, Penguin,2008.

5. Eaton, M. Nature Materials 2007; 6: 251–253.


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BIOPHARMACEUTICALS– FROM NICHE TOMAINSTREAMby Gareth Williams

Introduction

Biopharmaceuticals are making an ever-increasing impact in the healthcare market. In recent years,

biopharmaceutical medicines have successfully made thetransition from niche players to multi-billion blockbusterdrugs. Global sales rose from $75 billion in 2007 to $87billion in 2008 and sales are forecast to continue to grow.For protein biopharmaceuticals, the main categories ofproducts include monoclonal antibodies, erythropoietins,insulins and interferons.

Marks & Clerk’s 2009 biotechnologysurvey focused on a number of key areasof particular relevance to stakeholders inthe biotechnology industry – fromentrepreneurs, to scientists, investors andacademics. This short report covers thesection on protein biopharmaceuticals.

Mergers and consolidation

Most pharma companies have sought tocontribute protein biopharmaceuticals totheir drug pipelines from bespoke in-house R&D departments, wholly-ownedsubsidiaries, or via significant partnershiparrangements/investments with biotechcompanies.

For example, AstraZeneca has mergedCambridge Antibody Technologies(acquired 2006) with Medlmmune(acquired 2007) to create abiopharmaceuticals division; Merck hasestablished a biopharmaceuticalsdivision, Merck BioVentures, to provide apipeline of new and genericbiopharmaceuticals; Novartis hasstrengthened its biopharmaceuticalscapabilities by partnering with Lonxa andMorphoSys.

Yet the research shows that the view fromthe biotech community is somewhatdivided. Only 59% of respondents assert

that consolidation would be beneficial,meaning that a significant minority donot agree.

Thus, where consolidation leads to linksbetween biotech and pharma wascompanies, the involvement ofpharmaceuticals may be welcome inenabling biotech companies to becomemore commercial. Indeed, 89% ofrespondents assert that traditionalpharmaceutical companies can assist withmanufacturing and large-scalecommercialisation.

Yet this enthusiasm for biotech to learnlessons from major pharma wastempered by the realisation that thiscould lead to a loss of independence forthe industry. 83% of survey respondentsconsider that the combination of thecurrent funding squeeze and theincreased interest from pharmacompanies will shrink the independentbiotech sector by the end of therecession.

Patents

As discussed later in this section, patentsplay a crucial role in securing funding forbiotech companies to develop proteinbiopharmaceuticals. What may emerge isthat the R&D, or the patents on that R&D,become the battleground for finance.Notably, 93% of respondents believe thatin the current economic climate investorsare increasingly securing their investmentagainst IP rights or taking larger equitystakes.

However, it has to be remembered thatpatents are monopolistic – theirjustification is that they encourageinnovation. Though the marketplace fortherapeutics is vast and ever growing, acontraction in the number of biotechcompanies coupled with a shortfall ininvestor cash could mean thatmonopolistic patent rights are held by asmall number of cash rich companies.

Will this scenario best serve society’sneeds for developing new therapeutics?We have already seen initiatives like the“orphan drug” provisions. When thecurrent recession is over, schemes toencourage innovation in narrowlyprofitable markets could become morefrequent.

GARETH WILLIAMS is anaccount executive ofMarketforce Business Mediaemail:[email protected]


Marketing approval andbiosimilars

Protein biopharmaceuticals arehighly complex molecules producedvia manufacturing processes thatoften use living biopharmaceuticalalmaterial. In view of the complexityof the products and the fact that themanufacturing process can lead toheterogenicity, specific regulatorymechanisms have been adopted toensure protein biopharmaceuticalsproducts meet necessary quality andsafety criteria.

Striking the balance between safetyand supporting drug development isessential. Notably, 89% of therespondents consider that greatercertainty is needed for the approvalof biopharmaceuticals, showing thatregulatory mechanisms are notsatisfying industry needs.

Moreover, in recent years severalmajor protein biopharmaceuticalshave gone off-patent, opening thedoor to generic manufacturers togain a share in the market.Biosimilars (or “follow-onbiopharmaceuticals”) are copycatbiopharmaceuticals drugs. Themarket for biosimilars is rapidlygrowing as a consequence of thelapse of patents rights, and alsopublic policy in encouraging thedevelopment of cheaperalternatives to branded products.

Encouragingly, the survey revealsthat on balance 75% of industryconsider the emergence ofbiosimilars as a commercialopportunity, yet 71% recognise in aclimate already dogged by fundingand regulatory woes, as well asincreased political pressure, theemergence of generic competition isa growing challenge for originators.Notably, nearly three-quarters (72%)argue that insufficient incentives aregiven to reward the R&D ofinnovator firms.

While the research shows hugeoptimism among the industry, with81% believing the rise of genericswill result in more affordable

healthcare, adequatelycompensating innovator companiesemerges as a concern. 68% believethe legislation should providegreater reward for proteinbiopharmaceuticals products thanfor traditional drug products, due tothe longer time and greater expensein bringing these products tomarket.

Patenting of proteinbiopharmaceuticals

Current patent system

As a result of the considerable delayand expense of developing newbiopharmaceutical medicines, inmany cases the IP portfolios ofbiopharmaceuticals companies areoften their main means of attractinginvestment , and indeed their mainasset. Hence a strong patent systemsand a clear IP strategy are of keyimportance, particularly in thecurrent climate.

Yet the research shows thatrespondents lack confidence in theIP systems in Europe and the US –the very frameworks used to rewardinnovation. Only 57% describethemselves as confident in thepatent system at a European level,rising to 64% at the US level.

Against this background, whenasked about the establishment of aEuropean Community patentsystem, a clear majority of 80% ofrespondents indicate that thereaction of a common patent wouldbe beneficial for the biotechindustry. Certainly, a EuropeanCommunity patent system shouldoffer considerable costs savings overthe presently fragmented (in somerespects) route to obtaining patentprotection throughout Europe. Weresuch a system coupled with acentralised European Patents Court,then the cost of litigation wouldlikely be reduced, though anybenefit of “doubt and delay” forpatents would be minimised.Notably, little over a third (37%)

expect the common patent tobecome a reality, likely indicating afrustration between what theindustry feels would be beneficialand achievable, and the level ofdevelopment it expects at a co-ordinated European level.

Protein biopharmaceuticals offergreat hope in the development ofhighly-specific therapeutics, as wellas gaining importance as majorrevenue sources for the largepharmaceutical companies, but theneeds of both generics andoriginators will need to be met inwhat is a very fragile market.Ultimately, it may be the case thatpharma companies may play a keyrole here in bringing new proteinbiopharmaceuticals to market, tothe benefit of all.

IP strategies for proteinbiopharmaceuticals

Over two-thirds (68%) of the surveyrespondents think that the IP systemshould more generously reward thebiotech industry to compensate forthe greater expense of bringingbiotech products to market whencompared to traditional drugs.

Indeed, given the very large delay inbringing new medicines to market,often a “first generation” patentcovering a proteinbiopharmaceutical will be headingfor expiry not long after the producthas established a firm marketpresence. Against this background,what strategies can be used tosecure further IP protection?

A starting point is obtaining a patentterm extension. In Europe, theSupplementary Protection Certificatescheme can give up to an additionalfive years of patent-like protection tocompensate for delay in obtainingmarketing authorisation formedicinal and veterinary products.In the USA patent term extensionsare also available.

By implementing an IP strategy tocontinuously monitor the research

BBIIOOPPHHAARRMMAACCEEUUTTIICCAALLSS –– FFRROOMM NNIICCHHEE TTOO MMAAIINNSSTTRREEAAMM ((CCoonntt..))


required to bring the proteinbiopharmaceutical from thelaboratory to the marketplace, itwill usually be possible to obtainfurther patents that protectinnovative modifications. These aresometimes referred to as “patentthickets”, although the title canprovoke unwelcome reaction (seesection 4 on the EU commissionenquiry).

For example, optimising proteinfunction, enhancing MAb binding,or reducing immunogenicity may becovered by later filings. Also, celllines used to produce the proteinbiopharmaceuticals could bepatented, as could methods ofmanufacturing the protein. Any one

of these subsequent patents couldprovide an invaluable furtherextension to patent protection,often when the proteinbiopharmaceutical is in themarketplace and sales are close topeaking.

Finally, it is important not tooverlook the protection afforded byregulatory bodies, referred to asdata or marketing exclusivity. Incertain countries, regulatoryauthorities are not permitted toreference data submitted by theoriginal marketing authorisationholder for a prescribed period oftime. This is relevant if a generic orbiosimilar manufacturer applies forabridged marketing authorisation.

In certain countries, there may befurther period of marketingexclusivity as well.

This annual survey was made byMarks & Clerk, one of the world’sleading intellectual propertyconsultants. Over 360 executives,scientists, academics and investorsresponded to an international onlinesurvey concluded in May 2009. The2009 report brings together keyfindings of the survey and the role ofintellectual property – mostsignificantly patents, to the biotechsector.

For a copy of the research findings,contact Joanne Colton [email protected]

BBIIOOPPHHAARRMMAACCEEUUTTIICCAALLSS –– FFRROOMM NNIICCHHEE TTOO MMAAIINNSSTTRREEAAMM ((CCoonntt..))

Pharmaceutical Industry Advanced Training (PIAT) – Accredited Professional Developmentfor the Pharmaceutical IndustryCareer development and progression for staff in the industryand ancilliary organisations is as important for employers as employees. PIAT programmes are unique in their distance learning format, and have contributed to industry success for nearly 20 years. Modules are written by experts based in major Pharma from UK, Japan, Europe, Asia and academia, and are routinely updated. The programmes have a flexible structureof free standing modules.

Entry options: a minimum of an HND is usually required for a Diploma, and a degree level scientific qualification is usually needed for an MSc.

The five PIAT programmes are:

Industrial Pharmacy• Clinical Trials• Toxicology• Pharmaceutical Microbiology• Pharmaceutical Business and Development•

University awards include module credits, 15 per module, a Diploma for 8x15 credits, and an MSc is gained after the Diploma, plus Dissertation of 60 credits, making a total of 180 credits. The degree awarded for this is an Industrial Pharmaceutical Sciences MSc. Distinctions are awarded for marks of > 70% in all the modules and the Dissertation, and 12 have been awarded over the last 4 years.To date there have been over 200 MScs, and 3000 individual modules gained in the PIAT programmes. These programmes consist of distance learning modules of 15credits each.Course fees - £1,295 per module £11,655 for the MScEnquiries: [email protected] find out more, including the brochure, student handbooks, examples of module content, and newsletters please see

www.manchester.ac.uk/pharmacy/postgraduate/taught/piatSchool of Pharmacy & Pharmaceutical Sciences, The University of Manchester, Manchester M13 9PT, UK


HENRIK EJSING is managingdirector of Watson-MarlowFlexicon, Copenhagen,Denmark.email: [email protected]

The filling capacity depends on the size ofthe pump and with that the range oftubes to select from – see Figure 2. Inhigh speed filling applications severalpumps are installed on the same line co-working in parallel or serial mode. A bigpump would in theory be able to carryout the task, but small pumps haveproved more accurate.

The filling speed can easily be adjustedby varying pump speed. This can benecessary if the product has a tendencyto foam or in order to avoid splashing,which causes unwanted stains on theinside of the vials after freeze drying.Foaming and aeration can also bereduced by changing the acceleration forramping up and down while maintaininga high flow rate.

Accuracy

Figure 1 shows a peristaltic pump withtwo rollers, which is the standardconfiguration often used for flowoperations. For applications fordispensing biopharmaceuticals accuracywill be of vital importance and in thiscase more complex configurations of theperistaltic pump will usually be chosen.

There is a natural connection betweenaccuracy and pulsation and the morerollers the lesser the pulsation. Of coursethe size of the rotor imposes a limitationon the number of rollers, there is roomfor. However this can be solved by using adouble rotor with six rollers each – offsetwith respect to one another. The twotubes are connected on the pressure-sidewith a Y-piece and the solution is in

The peristaltic principle

The human intestine is in fact aperistaltic pump as muscle contractionspush the food forward through thebowels. The corresponding technicalsolution consists of a tube, which issqueezed flat by a roller and then thecontent of the tube is pushed forward –see Figure 1.

Behind the roller the tube will acquire itsnormal shape because of the plasticmemory. In this way a vacuum is createdand hence the tube is refilled and readyfor the next squeezing.

As you can see the tube is actually thepump. This fact constitutes the veryspecial qualities of the peristaltic pumpresulting in unique advantages in relationto production in the biopharma industry:

� No cleaning of the pump – the tube isdiscarded

� Reduced cleaning validation

� No risk of cross-contamination

� Change over time less than fiveminutes. Load new tube, purge andcalibrate.

The modern peristaltic pump is moreoverdesigned with the built-in possibility ofusing different sizes of tubes. This meansthat the same pump as an example canfill volumes from 0.1 ml to 250 ml simplyby changing the tube size.

PERISTALTIC PUMPS –AN ANSWER TOINCREASING DEMANDSWITHIN THEBIOPHARMA INDUSTRYby Henrik Ejsing

Peristaltic pumps have proved superior to other pumps inmany respects especially in the biopharma industry and

the implementation of peristaltic pumps is a growingmarket in the industry. Augmented needs for safetyprecautions and flexibility are causing increased focus onthe peristaltic pump as a viable alternative to traditionalpump technologies.

Figure 1. The principle of the peristaltic pump.


practice working like a rotor with 12rollers resulting in a pump withpractically no pulsation, see Figure 3.

Combined with precision motorsand specially developed dispensingsystems the peristaltic pump meetsfill volume accuracy at +/- 0.5% forfill volumes as small as 0.5 ml. Aparticular feature on manyperistaltic pumps is the possibility toreverse the rotor slightly after thefilling sequence in order to avoiddripping from the filling needle.

Peristaltic pumps for fillingapplications generally operate atlow pressure and micro fills areexecuted i.e. down to approx. 1.3bar of pressure. That is whyperistaltic pumps are ideal forhandling shear sensitive products.

For filling applications requiringhigh accuracy, validation of thefilling accuracy is of vitalimportance and there are differentways to go. Most companies do aprocess qualification where basedon filling tests it is decided how tocontrol the process in terms of setup procedures, initial tests and ongoing process control.

For instance it is always importantto run a new tube dry for approx. 1minute to warm up the tube and toactivate the mechanical abilities. Ifthis task is not performed, changesin flow rate will be seen over the first20 minutes of filling and without a100 % check weighing you wouldconsider the process “out of control”.

Process control is normally done

PPEERRIISSTTAALLTTIICC PPUUMMPPSS ((CCoonntt..))

Figure 2. Filling capacity by type size for two different pump sizes.

Figure 3. Pulsation as function of number of rollers. To the right a pump head with 12 rollers.

based on sample checking, but it isbecoming increasingly normal to doin line check weighing, where themeasures feedback directly to thepump for recalibration. This resultsin a very high level of control andaccuracy in the process of filling.

The tube

It goes without saying that choosingthe tube is of the outmostimportance for the performance ofthe pump. First of all, the choice oftube material is critical asmechanical as well as chemicalcharacteristics are inherent in thematerial. The product-resistance ofthe tube is meant to preventcontamination of the product anddamaging of the tube, while the

shore and the plastic memory of thematerial ensure homogenous andprecise dispensing. The mostcommon tube is the peroxide- orplatinum cured silicone tube whichcombines a relatively low cost withgood mechanical abilities.

For some applications it is crucial tochoose a tube that has been bakedto get rid of residuals fromextruding and curing the tube.

The lifespan of the tube varies withthe application. Most suppliers ofsilicone tubes would guarantee a

lifespan of 40 hours whenrequirements for filling accuracy arehigh. The tube can within thelifespan be autoclaved 4 to 5 timeswithout problems but most users ofperistaltic pumps in biopharmaindustry normally use a tube onlyonce to avoid cleaning and risk ofcross contamination. In many casessingle use will also be the most costeffective solution.

Ease of use

Most peristaltic pumps are easy touse. Typically they are part of fillingsystems with built-in in-lineweighing and auto calibration, andthe operator can concentrate onloading and off loading of vials,bottles or syringes.

In productions with many differentoperators and multiple-shiftproduction peristaltic pumps arepreferable because the pumps areeasy to use and the principle ismanageable and easily understood.


PPEERRIISSTTAALLTTIICC PPUUMMPPSS ((CCoonntt..))

Figure 4. Filling accuracy with fixed calibration procedures.

1ml accuracy test with recalibration after every 1,000 fillings

Filling

volum

e (%)

+1.00

+0.75

+0.50

+0.25

0.0

–0.25

–0.50

–0.75

–1.00

1 8 15 22 100 600 1300 2000 2700 3400 4100 4800 5500 6200 6600

Number of fillings

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gmp revıew is the first newsletter dedicated to the analysis of international pharmaceutical regulations and providing informed comment on good manufacturing practice.

Researched and edited by an expert team, gmp revıew will provideyou with a clear, practical guide to the often complex and jargon-ridden regulations that are continually being produced.

See our website for details or call +44 (0)1428 752222

STABILITY PROGRAMSNEED TO BE RE-INVENTEDBy Patrick Crowley

One has to sympathize with Johnson & Johnson. A volatileresidue on wooden storage pallets, purportedly

tribromoanisole, a breakdown product of a chemical usedto treat wood, was adsorbed on to Tylenol Caplets andother OTC products, leading to complaints of a moldy odor,nausea/pain and product recalls in the US.www.reuters.com/article/idUSTRE5BS2L820091229

This seems to be the “one-in-a-million”incident that conventional stabilityprograms would rarely, if ever detect!J&J’s announcements and recall seem tohave been exemplary, in the light of thesingle-digit level of complaints of GIdisturbance. A “when to recall” decision isnotoriously difficult if the volume ofcomplaints is around “noise level”,particularly as low levels of complaints of“nausea and stomach pain” are notunusual with many products. Iforganizations recalled product followingeach such report (many of which can beoutlandish) there would be few medicinesleft to treat patients.

The incident may raise wider issues.Pallets, like those at the J&J facility areprobably used by many otherorganizations to stack food, nutritionalproducts, beverages, etc. Can the samevolatile residues contaminate suchproducts? Foods contain carbohydratesand other components that are also usedas excipients. These probably have similaradsorptive capability for volatiles asmaterials in medicinal products.Packaging may be equally, if not morepermeable to vapors. Nutritionals utilisethe same excipients, containers,packaging accessories as Ethical Drugs. Itwould be good if a collaborative programwere to consider the implications for suchproducts. J&J have probably nowaccumulated expertise in detecting andquantitating such contaminants, as wellas acumen in associated “root cause”investigations. Co-operation and sharing

such expertise could be initiated andspearheaded by the organization whosemission is to improve the health of allAmericans, viz the FDA.

But that has not happened. Instead, theAgency quickly defaulted to “blamegame” mode and issued the usual“warning letter”. www.fda.gov/ICECI/EnforcementAction/WarningLetters/ucm 197811.htm.

Investigations to establish the cause ofthe contamination were probably longand arduous. Scientists and otherpersonnel must have spent many longdays establishing root cause. The reward?– a warning letter ! One can be cynicaland think that earlier notification by J&Jwould have elicited similar castigationthat “root cause had not beenestablished”. Will there now be a knee-jerk “pallet stability” requirement forfuture filings? Don’t bet against it.

What are the take-homemessages?

Drug product stability and componentinteractions never fail to surprise andrequire constant diligence, awareness andexcellent science to predict and control.

Mandated stability requirements, beinglarge tabulations of data, generated overmany months and years rarely if evermitigate the risk of such surprises.

It is time to redefine what constitutesgood stability practices. Good stabilitystudies should be designed to get toknow the drug in terms of its chemicaland physical propensities for degradationand interaction (particularly in the state ittakes in the dosage form: not justmechanistic and kinetic evaluations insolution). Knowledge of the materialswith which the drug is compounded isalso vital (numbers of excipients arerelatively small). We also need to “know”the packaging materials (and yes, eventhe pallets, the volatiles that mayemanate from lacquers and coatings inwarehouses, etc.). For too long the focuson packaging materials has concernedcapability to protect (with meaninglessWVTR requirements in pharmacopoeias):too little attention is paid to capability to“contaminate” due to their being a sourceof agents that can interact with

PATRICK CROWLEY is Head ofCallum Consultancy –Pharmaceutical IndustryConsulting & Services, basedin Devon, Pennsylvania, USA. email:[email protected];tel: +1 610 999 2434.



components or residues in thedosage form or delivery device.

“Stability” evokes images of multipletables of “all the same data” amongRegulatory Affairs professionals andof testing that most probably willproduce “the same” results amonglaboratory scientists. In a word“boring” and no prizes for guessingwho mandates the generation ofsuch data. Paradoxically, stability is

seen by many analytical scientists asonly becoming interesting when anincident mandates in-depth studiesand creative chemistry.

It’s time to re-assign “good science”status to stability studies so thatorganizations (and academicinstitutions) can once again studybehaviors in depth and use theaccumulated knowledge tocreatively assign use periods, storage

cautions and appropriate packagingto safeguard the quality ofmedicinal products.

Allocating blame post-the-event isall very well but at times we need tosee the mote in our own eye. It’stime to re-think approaches tostability and incorporate genuine“QbD” in our stability programs!

Are you listening ICH?

SSTTAABBIILLIITTYY PPRROOGGRRAAMMSS NNEEEEDD TTOO BBEE RREE--IINNVVEENNTTEEDD ((CCoonntt..))

Industrial Pharmaceutical MicrobiologyStandards & Controls

Editors: Norman Hodges and Geoff Hanlon“An exceptional and unique

publication in this field”Microbiologist – September 2007

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Special supplements

Regularly updated

Pharmaceutical Quality Group PublicationsThe Chartered Quality Institute’s range of Pharmaceutical Quality publications are now available to Industrial Pharmacy readers through Euromed Communications.

These include its Pharmaceutical Standards series (PS 9000:2001, PS 9000:2002 and PS 2004) and guidebooks concerning pharmaceutical quality issues.

For details and to purchase, please go to the Euromed website:

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Introduction

The current review period has seena number of changes in theregulation of medicines andregulatory guidance in both the USAand in the EU. The most significantof these would appear to bechanges to the EU GMP guide andstandards for securing the drugsupply chain (FDA). MHRArequirements relating to risk basedinspections and returns of non-defective refrigerated product arealso of significance.

United States of America

New and UpdatedRegulatory Guidance

The FDA has issued new andupdated guidance covering thefollowing topics:

� Standards for Securing the DrugSupply Chain—StandardizedNumerical Identification forPrescription Drug Packages.

� Guidance for Industry, Q4Bevaluation and recommendationof pharmacopoeial texts, generalchapters for use in the ICHRegions – Dissolution/Tabletfriability/ Polyacrylamide gelelectrophoresis.

FDA has announced

� A new programme known asFDA-TRACK (Transparency /Results / Accountability/Credibility / Knowledge). A newsystem for measuringperformance at FDA.

� The tightening of controls onoverseas manufacturers ofmedicines and on global supplychains.

REGULATORY REVIEW Review of major developments in GMP in the EU and USA,

February to May 2010

by Malcolm Holmes

Europe

EU GMP Guide

The European Commission hasproposed the following updates:

� Revision of Annex 6 to Part I ofthe EU GMP Guide – Manufactureof Medicinal Gases – effective 31July 2010.

� Revision of Annex 13 to Part I ofthe EU GMP Guide – theManufacture of InvestigationalMedicinal Products (IMP) –effective 31 July 2010.

� A draft revision to Annex 2 (Manu -facture of Biological MedicinalSubstances and Products forHuman Use) as a consequence ofthe restructuring of the GMPguide and the increased breadthof biological products such astransgenic derived products andthe Advanced Therapy MedicinalProducts (ATMPs).

� A draft guideline on Real TimeRelease Testing which is intendedto replace the current guidelineon parametric release.

� A draft guideline on the require -ments for Quality Documentationconcerning biological IMPs usedin clinical trials.

Products

The European PharmacopoeialCommission has:

� Conducted a survey on thepotential use of reverse osmosisfor the production of Water forInjection. Results are not yetavailable

� Issued a proposal for a newexpression of acceptance criteriain the test for related substances

which allows for a quantitativedetermination to be made in linewith ICH guideline Q3A (R2).

� Issued revised monographs forheparin under the rapidimplemen tation procedure.These will come into force onAugust 1 2010.

MHRA

The MHRA has issued:

� A requirement to communicatesignificant changes betweeninspections in its risk-basedinspection programme.

� An updated policy on returns ofnon-defective refrigerated products.

� Frequently asked questions (FAQ)on the importation of medicines.

International

API

EMA/FDA/TGA have agreed to holdregular teleconferences to maintainprogress on the topic of strategies toenhance assurance of the quality ofactive pharmaceutical ingredient(API) manufacture and distribution.

PIC/S

The PIC/S has created an example ofQuality Risk Managementimplementation.

PIC/S has also issued a notice of apossible application from HongKong’s Department of Health forPIC/S membership.

For further information on these andother topics we suggest you refer to thewebsites of relevant regulatory bodiesand to current and past editions of“GMP Review News” published byEuromed Communications. To subscribeto this monthly news service [email protected]


2010 General Assembly ofEIPG in Milan, Italy

The 2010 General Assembly ofthe EIPG was held in Milan

on the 15-16th May. During themeeting, the Association forIndustrial Pharmacists ofBulgaria was welcomed as anew member of the EIPGsubject to receipt of thenecessary documentation. Thiswill become available aftertheir inaugural meeting later inthe year. Valentina Belchevawas congratulated on her hardwork in establishing a nationalassociation.

Election of the Bureau

The member from Great Britain,represented by Gino Martini was re-elected as President and themember from France, in the name ofJean-Pierre Paccioni, was re-electedVice-President Finance (Treasury) .The Belgian member, represented byKristina Bindus, was elected as Vice-President European Affairs (Externalaffairs delegate) for the next 2 years.The Swedish member, represented byPar Tellner was co-opted to theBureau for one year as Vice-PresidentEducation and Careers.

Representatives from sisterEuropean Associations, PGEU(community pharmacists), AEHP(hospital pharmacists) and EAFP(colleges of pharmacy) attended ourmeeting as observers.

Contact with the EMA

A report of the EMA meeting with“interested parties” by PieroIamartino demonstrated thecontinuing large number of pendingGMP related issues. Jane Nicholsonreported that submissions had beenmade by EIPG on the EMA conceptpaper for the revision of Chapter 7

of the GMP Guide and on Part IIIproposals for the Site Master Files.Some concern was expressed as towhether the costs that are beingabsorbed by industry with all therevisions to GMP in Europe arereally justified.

Supply chain security

A working group considered thelatest proposals for amendments toDirective 2001/83/EC to prevententry of counterfeit medicines intothe supply chain. Claude Farrugiaconsidered the latest proposals arean attempt to juggle the need toraise standards whilst trying tomitigate the cost of implementingthese standards. Half measures willbe worse than no measures becausethey will give a false sense ofsecurity he warned. Conclusionswere that legislation and itsimplementation will be a majorchallenge that must be undertakento protect public health.

Proposals for the future of the clinicaltrial supply chain were presented byPhilippe van der Hofstadt.

Consultation on theEuropean Commission’sReview of Directive2005/36/EC (recognition ofprofessional qualificationsdirective)

Two meetings have been held withthe Head of Unit 4 and staff at theDirectorate General for the InternalMarket and Services. The Bolognadeclaration and the place of theBachelor of Pharmacy were raisedby the Commission and apresentation on the need forMasters level education for allpharmacists was made on behalf ofEIPG by our Belgium Association,VAPI/UPIP.

EIPG is a partner in the educationconsortium, PHARMINE, which ispreparing competency based

curricula that will inform theEuropean Commission’s update tothe Directive. The projectcoordinator, Professor Bart Rombautfrom Vrije University attended ourGeneral Assembly and acted asrapporteur for a working groupreviewing industrial pharmacycompetencies and the need forAdvanced Masters and Diplomacourses.

Country reports

Price reductions on pharmaceuticalsresulting in lower margins and cutsin the number of employees in thepharmaceutical industry wererecurring reports from delegations.

Industrial Pharmacy in Italy

Dr Giorgio Bruno, Qualified Personfor Corden Pharma reported on theprofessional development of theQualified Person in the Italianpharmaceutical industry. Hisoverheads can be found on the EIPGwebsite: http://www.eipg.eu/

European PharmacyStudents Association(EPSA) Annual Congress

On behalf of EIPG, Claude Farrugiamade a presentation on theamendments to Directive2001/83/EC to combat counterfeitmedicines during the EPSA AnnualCongress held in Krakow, Poland on27th April. An interesting debatetook place among speakers whoincluded representatives from EFPIA(the European Federation ofPharmaceutical Industries andAssociations), GIRP (the organisationof pharmaceutical full-linewholesalers in Europe), and PGEU(Pharmaceutical Group of theEuropean Union, representingcommunity pharmacists).

Jane Nicholson, Executive Director EIPG

NEWS FROM THE EIPG


The following questions and responses are a selectionof those published on an open online discussion groupwww.pharmweb.net/gmp.html. The Forum serves as ameans of exchanging views on internationalregulations affecting the pharmaceutical industry.Readers are invited to contribute to the Forum.

Leak testing of BFS/FFS

QI would like to learn from your experience inperforming leak tests of BFS/FFS bottles.

What procedure is required to perform suchtests? Is there any equipment/instrumentavailable for leak testing of bottles? Is there aguidance document on this?

Response 1 – Vacuum leak test apparatus can be usedfor leak testing BFS/FFS bottles. Once your filling andsealing is complete, you have to keep those bottles in theVLT apparatus under high vacuum for a particular timeperiod and once the process is complete you have to checkthe volume by visual inspection or by weighing them.

Leaked vials will show a low volume level or lessweight than the standard one.

Response 2 – I am afraid that the “vacuum leaktest” as described here will be only appropriate forimportant leaks. The same for the “pressure test” whichconsist in firmly pressing the bottles (mechanically orby hand) and to inspect them for traces of liquid.

When it comes to microleaks, and because of theplasticity of the BFS/FFS bottles (PE or PP), the chancesof detecting a failing bottle by “emptying” it are notoptimised. Detection of leaks by measurement of gas(air or helium) entry/output is much more effective butalso much more expensive. You can also detectmicroleaks through the perturbation of an electro-magnetic field in which the container is placed (themethod was first developed by Nikkai Densok but youcan now find other manufacturers).

Change control

QI have revised our MPCR (Master Process andControl record). I need to know whether it is

absolutely necessary to file a change controleven though the changes that have beenincorporated are not process related and arepurely for the sake of simplifying the documentcontent?

Response 1 – Yes, all changes must be documentedby change control. Among other things, this allowsreaders in the future to follow the evolution of thedocument.

Response 2 – Absolutely yes. You need to recordthe change through your change control system.

If you don’t you could be on a very slippery slope –today you have just simplified the document (nochange control), tomorrow someone else makes whatthey think is a minor change (no change control). Andpretty soon your entire documentation system iscorrupted and useless.

Response 3 – I believe that to use or not to usechange control depends on what the Validation MasterPlan requires you to do. After all, any auditor wouldexpect you to follow what you have stated to be yoursite policy. Any departures from those “promises”would be regarded with concern.

If in your VMP you have documented satisfactorily howyou intend to deal with any GMP documentrevision/change and you carry out that statedprocedure, then I see nothing that suggests any breachof GMP has occurred.

In my experience of well over 30 years in thepharmaceutical industry such intended physicalchanges must undergo representative and structureddebate within the business groups that are planning tomake such changes and be approved by the QA groupthat will be called at audit to defend/explain them.

However, it is also important to recognise that auditorsare also human and may have interpretations of the GMPrequirements which are perhaps different from yourown. It isn’t sufficient to simply assume they will approveof all your VMP detail (and therefore of any change youmay conduct under the details you have documented).

The site must be fully prepared in advance of any auditto defend the decisions it decided to take in order todelivery GMP compliance.

Finally, successful GMP delivery is not something to belearned by rote. Its achievement is always predicatedupon the assumption that common sense will beapplied.

Equipment usage log

QA usage log of major equipment shall bemaintained. How can we categorise

major/minor equipment? For example, do weneed to maintain a usage log for pH metersused in production?

Response 1 – Industry practice is to maintain usagelogs for all equipment that must be calibrated orotherwise maintained. Impact on the product, ratherthan cost or size of the equipment, determineswhether the equipment is “major”.

PHARMACEUTICAL FORUM


Yes, there must be a usage log for a pH meter andprobe used in production. The log must record in GMPfashion what batches the equipment was used for. Itshould also record, or reference another recordingdocument, each standardisation of the pH meter,including the batch identification of eachstandardisation buffer solutions used. (Your SOP shouldguide on the pHs of the buffers used, which generallyshould bracket the target pH range. Your SOP shouldalso guide on what the acceptable performance of thepH probe is, which is usually the slope of theresponse.) The actual performance of the probe duringstandardisation, and that it passed or did not, are alsoto be recorded in the usage log.

Response 2 – Generally people identify equipmentas critical (may be termed major) and non-critical (maybe termed minor). Then obviously you should maintaina log book of all critical instruments as those areinstruments which have a direct impact on yourprocesses. For non-critical equipment, only amaintenance and calibration log my be sufficient.

Response 3 – Your question comes at a goodmoment for me. I am currently auditing a companyand every piece of equipment requires the staff torecord the time started to use and the time ofcompletion. This includes pH meters and evenanalytical balances. This seems to be completelyridiculous (particularly as they also then need multiplesignatures for this).

In other words they have converted simple things likepH and weighing into a user log.

Response 4 – I agree with the previous responderthat some companies manage to interpret GMP as“Great Mounds of Paper”. The silly situation is reachedwhere the process holds up the smooth flow of paper.

However, I’m not in complete agreement with nothaving log books for pH meters and balances.

If the procedure is to buffer (standardise) the pH meterdaily and not before each pH check, there should be arecord that this has been carried out – a simple logbook. If there is more than one pH meter in the lab,noting which measurements have been carried out onwhich meter can make life easy should there be aproblem.

A similar argument can be made for balances.

Most importantly, keep it simple and the informationcan be recorded in a few seconds. All that is required isdate and either standardisation (daily check) or LotNumber.

PPHHAARRMMAACCEEUUTTIICCAALL FFOORRUUMM ((CCoonntt..))

Sterile powder injection in polypropylenecontainers

QI would like to know whether lyophilisedsterile powder injection materials can be

packed in polypropylene containers under sterileconditions and sterilised by ethylene oxide?

Response 1 – There are two issues for consideration:

1. EtO is a surface sterilant. How would you validatethe process for the material inside the container?

2. The levels of residual EtO/EtCH, etc. remaining fromthe processing will need to be very closelymonitored and controlled.

Response 2 – Wow! Your project is risky. Certainlypolypropylene containers could be filled with a powderbut this powder should be sterilized beforehand(ideally with gamma-irradiation). This is becauseethylene oxide is a gaseous sterilant agent known toexert its action mainly on surfaces. If you read Annex 1of the EU-GMP guide you’ll see that point No. 105discourages the sterilization of powders with such agaseous agent. Sorry, but I have some doubt on thesuccessful issue of your project.

Purified water

QWe order demineralised water from anexternal supplier and it’s delivered to us in 1L

containers. Our supplier doesn’t performmicrobiological testing routinely. My question is:how should I ensure that this water complies withthe requirements for Purified Water (PH.Eur)? Dowe have to perform microbiological examinationfor each container and each time? And, for howlong will this water remain “purified”?

Response 1 – Is the filling operation done in cleanand closed conditions? Is the container re-usable? Isthe water generated in a single batch? During theinitial study you can perform 100% sampling andtesting. And based on the supporting data you mayreduce the number of test samples. My suggestion is touse the water within 48h from the time of filling. Anyof this should be supported with a validation study.

Response 2 – Since you purchase the water from asupplier, you should have/ask for a CoA of the purifiedwater from the supplier. And your QA department shouldaudit the supplier and approve him as the qualifiedsupplier. The first time you receive the water, it should betested for microbiology and in time, based on thestatistical data, you can reduce the quantity for testing.

Readers are invited to send their Q&As towww.pharmweb.net/gmp.html

job vacancies

Head of PharmacovigilanceA fantastic newly created opportunitywith a growing Pharma for a GMCregistered Physician with strongexperience in Drug Safety.Location: Berkshire/Middlesex, UKSalary: £85,000 – £90,000 per annum+ extensive benefits packageReference: HM/46590/EIPGContact Harriet Maidman: 0207 940 2103, [email protected]

Clinical Development AdvisorExcellent hybrid role in Clinical andMedical Affairs for candidates with aPharmacy background Location: Surrey, UKSalary: £40,000-£50,000 per annum +excellent benefits packageReference: HM/46410/EIPGContact Harriet Maidman: 0207 940 2103, [email protected]

Pharmacovigilance SpecialistUrgent requirement for 3month+contracts in diverse safety contractsgaining strong experience in a globalorganisationLocation: Middlesex/Surrey, UKSalary: £24-£28 per hourReference: HM/46573/EIPGContact Harriet Maidman: 0207 940 2103, [email protected]

Klinikreferent -Hannover/BremenOur client is an internationalpharmaceutical company specialisingin unmet therapeutic areas.Location: Germany – home basedSalary:€40,000 - €50,000 p.a. plus 20%bonusReference: MS/46042/50/EIPGContact Marketa Smelhausova,[email protected], 0044 (0) 207 940 2103

Klinische Leadmonitor -Munich, Berlin, FreiburgThis an exceptional role, ideal for anexperienced Lead CRA who is lookingto get the right experience for ProjectManagement role. Location: Germany – home basedSalary: up to €60,000 p.a.Reference: MS/46318/50/EIPGContact Marketa Smelhausova,[email protected], 0044 (0) 207 940 2103

Senior Clinical Data Analyst –BerlinAn exceptional opportunity has comeup for an experienced Clinical DataAnalyst to join one of the largest CROsas a Senior Clinical Data Analyst.Location: Berlin, GermanySalary: up to €45,000 p.a.Reference: MS/46500/50/EIPGContact Marketa Smelhausova,[email protected], 0044 (0) 207 940 2103

Clinical Project Manager – TOPPHARMAOur client is one of the leadingpharmaceutical companiesheadquartered in Germany. You will bethe key member for managing riskassessment and mitigation plans and fororganising the logistics of clinical studies.Location: GermanySalary: up to €65,000 p.a. – €70,000 p.a.Reference: MS/46060/50/EIPGContact Marketa Smelhausova,[email protected], 0044 (0) 207 940 2103

Drug Safety Director –Vaccines!A fantastic opportunity has arisenwith one of the leading biotechnologycompanies for a Drug Safety Directorto join their site in Germany. This is achallenging opportunity that shouldnot be missed.Location: GermanySalary: up to €130,000 p.a.Reference: MS/45258/50/EIPGContact Marketa Smelhausova,[email protected], 0044 (0) 207 940 2103

Associate Director, RegulatoryDevelopmentHigh-level Regulatory ProjectManagement with Phases I to IVfocus, across Pharma and Biotech. 8+years’ experienceLocation: Cambridge, UKSalary: £70,000-£80,000 basic, plus carallowance and excellent benefitsReference: JT/46205/7/EIPGContact Julian Turner, 0207 940 2108,[email protected]

Regional Manager RegulatoryAffairsLeading CRO. Line management ofRegulatory Project Leads andRegulatory Officers. ClinicalRegulatory Affairs Phases II to IV. 5+years’ experienceSalary: Negotiable depending onexperience.Location: Eastern Europe based –flexible regarding locationSalary: Negotiable depending onexperienceReference: JT/46585/2/EIPGContact Julian Turner, 0207 940 2108,[email protected]

Regulatory Affairs – ProjectLeadsLeading CRO. Project Management.Clinical Regulatory Affairs Phases II toIV. Organising Regulatory Officers. 3+years’ experienceLocation: Western/Eastern Europebased – flexible regarding locationSalary: Negotiable depending onexperienceReference: JT/46587/3/EIPGContact Julian Turner, 0207 940 2108,[email protected]

Regulatory Affairs TeamLeaderLeading small Team. Development,Registration and Post marketingactivity. EU Procedures knowledge. 3+years’ experienceLocation: Essex, UKSalary: Circa £40,000 basic, plus goodbenefitsReference: JT/45706/42/EIPGContact Julian Turner, 0207 940 2108,[email protected]

NonStop Recruitment is a market leader in European pharmaceuticalRecruitment with specialist consultants covering major markets such asUK, Germany, Switzerland, France, Italy and the Netherlands. Theseconsultants recruit for all major roles within the pharmaceutical industry,including clinical research, quality assurance, sales and marketing,pharmacovigilance, business development and regulatory affairs.


Title: Regulatory AffairsProject Manager - CMCSpecialist Pharma. Development,Registrations and Post marketing –CMC expertise. 4+ years’ experienceLocation: Middlesex, UKSalary: Very competitive packageReference: JT/46566/18/EIPGContact Julian Turner, 0207 940 2108,[email protected]

Regulatory 6 months ContractRegulatory Contract, Post marketingand Life-cycle focus. 3-4 years’experienceLocation: West of London, UKSalary: £40-£50 per hour ratesReference: JT/46527/6/EIPGContact: Julian Turner , 0207 940 2108,[email protected]

Qualified PersonsNetherlands, ImpressivePackage A multinational with a facility in TheNetherlands has excellentopportunities for QPs who would liketo take on roles broader and moreinvolved than run of the mill QPpositions.Location: Amsterdam, NLSalary: €60,000-€80,000Reference: SK/44884/EIPGContact Stephen Kenny,[email protected], (0)20 7940 2105

Soon to Qualify QP? GainNiche Pharma Experience incSterileA niche pharmaceutical company inBerkshire have an opportunity for aQuality professional who has recentlyqualified as a QP or is due to qualifywithin the next few months.Location: Berkshire, UKSalary: £40,000 - £50,000 + Car +BonusReference: SK/42578/EIPGContact Stephen Kenny,[email protected], (0)20 7940 2105

IMP QP, ASSOC DIRECTOR,BROAD POSITION, BIOTECHIn the market place at present thereare a variety of opportunities for QPswith IMPs however there are few asrewarding or with the breadth ofresponsibility as this one. The client is a well known blue chipbiotech with an impressive portfolio. Location: Cambridge, UKSalary: £60,000 – £73,000Reference: SK/46340/EIPGContact Stephen Kenny,[email protected], (0)20 7940 2105

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JJOOBB VVAACCAANNCCIIEESS ((CCoonntt..))


28 August-2 September 2010 – Lisbon,PortugalWorld Congress of Pharmacy &Pharmaceutical Sciences 2010 and70th International Congress of FIPwww.fip.org/lisbon 2010

SSEEPPTTEEMMBBEERR1-3 September 2010 – Nottingham, UKUK-PharmSci 2010: the Science ofMedicineswww.ukpharmsci.org

5-9 September – Brussels, BelgiumInternational symposium onmedicinal chemistrywww.ismc2010.org

14-15 September 2010 – Manchester,UKAnalysing and trending data to drivequality improvementwww.DBA-global.com

16 September 2010 – Basel, SwitzerlandPost-Approval Summit – practicalissues and considerationswww.basel.postapproval.org

20-24 September 2010 – Bath, UKFundamentals of GMP; a practicalapproachwww.phss.co.uk

21-22 September 2010 – Berlin,GermanyFormulating better medicines forchildrenwww.apv-mainz.de

Hard hitting web-based GMP training in thecomfort and convenience of your office or home(save on expensive and inconvenient travel:

These seminars are offered as web-based learning:

• Passing an FDA Inspection – Guaranteed• Managing the QC Lab in a GMP Manner• Fundamentals and Essentials of Validation• Effective Investigations and Corrective Actions• Effective Quality Assurance Auditing For full details and registration check our website at:www.globepharm.org/seminars.html/course

GMP and Quality System Consulting:

• With over 200 clients in 27 countries, we prideourselves that every single one of our clients haspassed an FDA inspection the very first timethrough (when they have listened to us)

• We have wide expertise in evaluating GMP andQuality Systems at your facilities and inperforming third-party supplier and contractmanufacturer audits

Let us assist you. Speedily and cost effectively. Contact us at: [email protected]

World Leader in GMP gap analyses,seminars and individual GMP training

27-28 September 2010 – Amsterdam,NetherlandsAmorphous Pharmaceutical Materialswww.pharmaamorphous.com

27-28 September 2010 – Amsterdam,NetherlandsPharmaceutical Co-Crystalswww.pharmacocrystals.com

29-30 September 2010 – London, UKQuality by Design: on a small budgetwww.management-forum.co.uk

OOCCTTOOBBEERR1 October 2010 – London, UKLinking pharmaceutical quality andpharmacovigilance systemswww.DBA-global.com

5-7 October 2010 – Paris, FranceCPhl worldwide www.cphi.com

14 October 2010 – Manchester, UKBest practices in microbiologicalcontrol and documentationwww.pharmig.org.uk

14-15 October 2010 – Prague, CzechRepublicQuality of medicines in a globalisedworld: dreams and reality www.edqm.eu

27-29 October 2010 – Barcelona, Spain13th APIC/CEFIC European Conferenceon active pharmaceutical ingredientswww.api-conference.org

DATES FOR YOUR DIARYJJUUNNEE

24 June 2010 – London, UK4th European Forum for QualifiedPerson for Pharmacovigilance (QPPV)www.diahome.org

29 June 2010 – London, UKA risk-based approach to medicinalproducts and medical devices – thecommon challenges for allstakeholderswww.topra.org

29 June-1 July 2010 – Nice, FranceImpurities, Impurities, Impuritieswww.management-forum.co.uk

JJUULLYY

10-14 July 2010 – Portland, USA37th Annual meeting & exposition ofthe Controlled Release Societywww.controlledrelease.org/meeting

13-16 July 2010 – Prague, CzechRepublicXIVth International conference onluminescence spectrometrywww.isls2010.org/contacts.html

26-30 July 2010– London, UKWorking through drug development –Management Forum’s Summer Schoolwww.management-forum.co.uk

AAUUGGUUSSTT

2-7 August 2010 – Glasgow, Scotland42nd IUPAC Congress, chemistrysolutionswww.iupac

european Industrial Pharmacy Issue 6 (June 2010)

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