european industrial pharmacy issue 22 (september 2014)

europeanINDUSTRIALPHARMACY

ISSUE 22 • SEPTEMBER 2014www.industrialpharmacy.eu

www.eipg.eu

features4 SUPPLEMENTARY PROTECTION CERTIFICATES:

OF CLARITY AND CONFUSIONThe law surrounding SPCs is difficult anduncertain. Three December 2013 judgments fromEurope's highest court clarify one issue butcreate several more.by Ian Moss

6 LIFE SCIENCES REPORT 2014: GENOME 2.0This article discusses the findings of the Marks &Clerk Life Sciences Report, which includesintellectual property trends in the genomemarket and patent analytics conducted insequencing technology, personalised medicineand synthetic biology.by Richard Gibbs

10 PHARMACOPOEIAL HARMONISATION: ANHISTORICAL PERSPECTIVEPharmacopoeial harmonisation has been aconstant process since 1864. This articlesummarises some of the key achievements andsuggests that the future lies in enhancedcooperation and work-sharing between thenational and regional pharmacopoeias.by Tony Cartwright

regulars3 EDITORIAL COMMENT16 REGULATORY REVIEW18 BOTTLED BROWN19 NEWS FROM THE EIPG20 EVENTS

2 european INDUSTRIAL PHARMACY September 2014 • Issue 22

europeanINDUSTRIALPHARMACYIssue 22 September 2014

ISSN 1759-202X

MANAGING EDITORSue Briggs

PRODUCTIONDave Johnson

SUBSCRIPTIONSJill Monk

EDITORIAL BOARDMichael AnisfeldClaude FarrugiaMichael GamlenLinda HakesJohn Jolley

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Cover photo: A model of a section of agenome (see Life Sciences Report 2014:Genome 2.0 on page 6)

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

The shape ofpharma to comeWelcome to the Septemberissue of European IndustrialPharmacy. As I pen thiseditorial, the last days ofsummer are passing away, andI hope that you all had theopportunity to enjoy a well-deserved break. Certainly, theindustry has shown no sign ofany lull in activity. Indeed, as Ilook over the events of thelast few months, I amreminded of Professor Luigi Martini’s predictionof pharma heading for the perfect storm yearsago. How right he was – this year’s events andthe events that they herald, in my opinion, arenothing short of cataclysmic. The defining activity for 2014 has to be the

breathless pace of merger and acquisitionactivity – and the best (or the worst?) is yet tocome. The year’s two most hotly debatedmergers still weigh in the balance, and arelikely to evoke high emotions in the playersinvolved, as well as in politicians and society asconcerns and scrutiny abound. My concern,and that of my colleagues on the Bureau, is theinevitable consequence to industrialpharmacists and other colleagues caught in thecross-fire of the moment and its aftermath. Ispeak of the loss of employment that follows,

notwithstanding all previousassurances, as streamlining andexpense curtailment areimposed on the new entities toensure that rising expenses anddemands for lower marketprices do not sink the ship on itsmaiden voyage. The fact thatsuch events are inevitable is oflittle consolation to the unsungheroes in the story of everymedicinal product – indeed,perhaps it is all the moresaddening that their potential

plight appears not to provoke the necessaryprophylaxis until it is too late. I cannot promise that EIPG can prevent all

this. To those who experience the doucheglacée of having to seek new employmenthaving donated years of their every thoughtand effort to making a difference in the qualityof life of patients, I can, however, promise thatEIPG is concerned and does care – collectivelyand individually – and will continue to do itsbest to support industrial pharmacists as theyseek their roles in tomorrow’s pharma.

Professor Claude FarrugiaVice-President Communications, EIPG

3european INDUSTRIAL PHARMACY September 2014 • Issue 22

editorial

CALL FOR ARTICLESDear Colleague

We hope you enjoy the European Industrial Pharmacy and find it both useful and informative.

We are currently seeking new articles for future issues of the journal and would like to inviteyou to contribute an article or review paper on any aspect of industrial pharmacy to thejournal. All issues of European Industrial Pharmacy are indexed by both Scopus and Embaseand thus are available through the listings for any other industrial pharmacist internationally.

BackgroundSince 1993, patentees in Europehave been able to extend the 20-year protection afforded by theirpatents for medicinal products byseeking the grant of asupplementary protectioncertificate (SPC). The grant of anSPC extends the protectionprovided by a patent by up to amaximum of 5 years. SPCs weredeemed necessary to offset thedelay in bringing medicinalproducts to market resulting fromthe need to obtain prior marketingapproval and are fundamental toensuring the financial viability ofpharmaceutical research anddevelopment. The EuropeanRegulation establishing the SPCsystem stated that without SPCs"the period of effective protectionunder the patent [is] insufficient tocover the investment put intoresearch". However, precisely whatcan be protected in this way isoften uncertain due to the wordingof the SPC Regulation, resulting innational courts making numerousreferences to the Court of Justiceof the European Union (CJEU) forguidance.This article deals with three

judgments given by the CJEU atthe end of 2013 and considers thestate of the law in their aftermath.

The 2013 judgments The grant of an SPC requires that

the relevant “product” is protected“as such” by a patent; there is avalid marketing authorisation (MA)in relation to the product; theproduct has not already been thesubject of an SPC; and the MArelied on is the first authorisation toplace the product on the market asa medicinal product. On 12December 2013, the CJEU gave itsjudgments in GeorgetownUniversity v OctrooicentrumNederland1, Actavis v Sanofi2 andEli Lilly v Human GenomeSciences3. The judgments considerissues to do with the requirementsthat the relevant product becovered by a basic patent in forceand that the product in questionhas not already been the subject ofan SPC. The referring Courts sought

guidance from the CJEU in relationto a total of 10 questions which theCJEU reformulated such that it onlyconsidered two.1. Can multiple SPCs be granted

based on the same basic patent?2. To qualify for SPC protection,

does the product have to beidentified in the patent claims by itsstructural formula or is it sufficient ifit is covered by a functional formulain the claims?In relation to Georgetown (inparticular), the failure to considerthe specific questions referred isdisappointing. In Georgetown, thereferring court had additionally

sought guidance regarding (i) theeffect co-pending SPC applicationshave on one another; and (ii) theeffect of surrender of an existingSPC including the applicable law,whether the effect is retrospectiveand whether it entitles a patenteeto seek a new SPC which wouldotherwise have been blocked.While the questions were phrasedsuch that answering them becameunnecessary, they deal withimportant issues which are likely togenerate additional references indue course.

Question 1The UK Intellectual Property Office(and other national offices) hashistorically been willing to grantmultiple SPCs in relation to thesame patent where that patentcovers multiple products (for whichMAs have been obtained).However, prior to Georgetown andActavis, the CJEU’s earlier cases(Medeva4, Biogen5 ) potentiallyindicated that only one SPC shouldbe granted per patent. In Actavis, Sanofi held a patent

protecting a class of compoundsincluding irbesartan, an anti-hypertensive. Also covered by thepatent were combinations ofirbesartan with other activeingredients, including anunspecified diuretic. On the basisof its patent and an MA grantedfor Aprovel (containing irbesartanalone), Sanofi was granted an SPCwhich expired in 2012. A furtherSPC was also granted on the basisof the same patent and a later MAgranted for CoAprovel (containingirbesartan in combination with thediuretic hydrochlorothiazide). Theeffect of CoAprovel is equivalent totreatment with separate tabletscontaining each active ingredient(the CJEU stated that there is nonew therapeutic effect). Actavischallenged the validity of the

european INDUSTRIAL PHARMACY September 2014 • Issue 22

SUPPLEMENTARYPROTECTION CERTIFICATES:OF CLARITY ANDCONFUSIONby Ian Moss

The law surrounding supplementary protectioncertificates is difficult and uncertain. Three December

2013 judgments from Europe's highest court clarify oneissue but create several more.

Ian Moss is an Associate in Hogan Lovells’ London Intellectual Property teamspecialising in hard IP.

4

SUPPLEMENTARY PROTECTION CERTIFICATES: OF CLARITY AND CONFUSION continued


second SPC, arguing that thecombination was not protected assuch by the patent.In answering question 1, the

CJEU noted the purpose of theSPC regime is “to compensate forthe delay to the marketing of whatconstitutes the core inventiveadvance that is the subject of thebasic patent”, not “the marketingof that invention in all its possibleforms” in combination with otheractives “simply referred to in thewording of the claims of the patentin general terms”, as to do sowould be contrary to therequirement to balance thepharmaceutical industry’s needsagainst those of public health andencouraging research. The CJEU’sjudgment concluded that apatentee in possession of an SPCbased on an innovative activeingredient which is protected assuch by the basic patent and anMA for that active ingredient aloneis able to oppose the use of thatactive ingredient alone or incombination. Further SPCs basedon a later MA for the same activeingredient in combination withanother active should only begranted where the additionalactive(s) are also protected as suchby the patent. Where this is not thecase, a new basic patent whichdoes protect as such thecombination may be the basis of anew SPC.In Georgetown, the university

held a patent to a humanpapillomavirus (HPV) vaccineutilising proteins isolated from theHPV-6, HPV-11, HPV-16 and HPV-18strains. In The Netherlands,

Georgetown applied for and wasgranted an SPC covering acombination of all four strainproteins (amongst other SPCs).However, an application for an SPCin relation to HPV-16 alone basedon the same MA was refused onthe basis that only one SPC shouldbe granted per basic patent. Considering the question, the

CJEU noted that, in principle, abasic patent protecting multipleproducts may allow for multipleSPCs provided there are relevantMAs. The CJEU reiterated that thepurpose of SPCs is “to encourageresearch in the pharmaceuticalsector by granting one SPC perproduct”, and that to findotherwise (i.e. that only one SPCmay be granted per patent) wouldbe to encourage multiple patentswhere one would suffice. The CJEUdistinguished Actavis on the basisthat both HPV combinations andHPV-16 alone were protected assuch by the basic patent. In thissituation, in which a basic patentprotects as such both acombination of active ingredientsand those active ingredients singly,and, where an MA in respect of thecombination exists, a patentee maybe granted SPCs for both thecombination and the individualactive ingredients. The judgments are perhaps fact

sensitive but, in both, the CJEUfocused on what products wereprotected as such by the patent indetermining whether that patentcould be a basis for multiple SPCs.

Question 2Prior to Lilly, CJEU case law hadmade clear that to be protected assuch by a basic patent the productmust be “specified”6 or“identified”7 in the claims. In Lilly,Human Genome Sciences held apatent for the protein Neutrokine-αand antibodies which bindspecifically to it. Lilly wished tomarket a pharmaceutical containingsuch an antibody, referred to astabalumab, and sought adeclaration that any SPC granted toHuman Genome Sciences on thebasis of an MA obtained by Lilly for

tabalumab would be invalidbecause it was not protected bythe basic patent. The parties’interpretations of“specified”/“identified” differedmarkedly, with Lilly arguing that, tobe protected as such, theformulation of tabalumab shouldhave been structurally defined inthe claims. The CJEU held that a functional

definition of the product in thepatent claims is sufficient for thepatent to be protected as such, ifthat definition, in combination withthe patent specification as a whole,relates “implicitly but necessarilyand specifically” to the product inquestion. Determination of whetherthis is so was held to be a questionfor national courts because thescope of a patent must (in Europe)be determined in accordance withEuropean Patent Conventionprovisions over which the CJEU hasno jurisdiction. As with“specified”/“identified”, thislanguage lacks clarity andunfortunately compounds the issueby creating two areas forinterpretation where previouslythere was one.

CommentFollowing the CJEU’s judgments inGeorgetown, Actavis and Lilly, it isclear that a patentee can obtainmore than one SPC per basicpatent where that patent protectsas such more than one product.Unfortunately, what is protected assuch is still unclear, indeed it mayactually be less clear than it wasbefore. This was recently illustratedby the UK High Court, which gaveits post-reference judgment in Lilly.Giving judgment requiredinterpretation and application of“implicitly but necessarily andspecifically” which provedchallenging, the Judge noting that“one thing the Judgment does notgive is the clear guidance which thereference was designed to obtain”.As the Judge granted permissionto appeal, the UK Court of Appealwill soon have opportunity to

SPC applications Number

Applications lodged 299

Granted 172

Entered into force 184

Expired 173

Lapsed 9

Invalid 7

Rejected 16

Data taken from www.ipo.gov.uk.

UK SPC figures, 1 January 2010 to31 June 2014

Continued on page 9

IntroductionIn the last year, there has beenplenty of activity in the life sciencesector with the Myriad andPrometheus rulings complicatingthe legal framework, governmentinvestments bringing energy to thesector and companies, large andsmall, making investments andindustry acquisitions. Since the end of the first era of

genome sequencing, the challengehas been to apply ourunderstanding to practicalapplications. It is not enough tosimply identify a particular gene asassociated with a disease, or to

identify genes coding for aparticular cellular pathway. Rather,we now have the ability to pinpointa specific genetic variation in aspecific patient, which can predictdisease progression and drugefficacy. We are now personalisingmedicine.Meanwhile, synthetic biology is

growing. The first commercialapplications of this are in theindustrial and fuel space, butbespoke designed drugs andentirely novel synthetic products arenot far behind.Linked to the surge in interest in

both personalised medicine and

synthetic biology are rapiddevelopments in the field ofsequencing. With the US$1000genome now almost a reality, thereare increasing expectations that newmethods of sequencing will furtherlower the cost and reduce the timetaken to elucidate the informationessential to both these disciplines.Marks & Clerk’s 2014 Life Sciences

Report reviews patent filing dataand geographical trends todetermine where the industry hasbeen and where it is going.

MethodologyThe 2014 Life Sciences Report isbased on data provided by CPAGlobal. Patent landscaping wascarried out for patent applicationspublished around the worldbetween 1 January 2003 and 31December 2013 relating to threeseparate areas of technology:sequencing technology,personalised medicine andsynthetic biology.

Personalised medicineThe development of personalisedmedicine has, in part, been fuelledby the need to supplement thosedrugs that are only effective intreating small proportions of thepopulation. Personalised medicineallows doctors to screen patients todetermine if they are likely torespond favourably to a particulartreatment and/or to tailor drugtherapies to patients. Of the top applicants in

personalised medicine, over half are

LIFE SCIENCES REPORT2014: GENOME 2.0by Richard Gibbs

In June 2014, leading international intellectualproperty firm Marks & Clerk published its LifeSciences Report 2014: Genome 2.0. The report looksat intellectual property trends in the genome marketand is based on patent analytics conducted in threeselected areas: sequencing technology, personalisedmedicine and synthetic biology. The data shows thatpublic research organisations are driving advances intothe study of genome-related technologies, with theprivate sector lagging behind. Further, the reporthighlights that despite over €1 billion of publicfunding coming from the EU for research intopersonalised medicine between 2007 and 2012, it isthe US public institutions that are leading the way inpersonalised medicine and synthetic biology. In thefield of sequencing technology, the data shows thatCalifornian giants Life Technologies and Illumina aredominating patent filings, but disruptive technologiesare emerging to challenge the status quo.

Dr Richard Gibbs BSc, PhD is a Chartered and European Patent Attorney based atthe Glasgow office of the international firm of intellectual property advisers, Marks &Clerk. Dr Gibbs advises clients in patenting and other IP matters in the field ofbiotechnology and has particular expertise in technologies relating to antibodies,vaccines, biologics, virology, bacteriology and molecular biology. He has workedwith all of Scotland’s major universities and is a regular speaker at IP conferencesand events. Dr Gibbs joined the patent profession after a period as both a researchscientist and a university lecturer having obtained an honours degree in medicalmicrobiology and a doctorate in immunology and microbiology from the Universityof Edinburgh.

Life Sciences Report 2014 Genome 2.0


LIFE SCIENCES REPORT 2014: GENOME 2.0 continued


public bodies and most are USresearch agencies, hospitals oruniversities (see Table 1). The National Institutes of Health

(NIH) lead the way in the field,applying for more than twice asmany patent families as the secondlargest applicant, Roche, since 2003.While the number of patentsapplied for by the NIH has fallenover recent years, others (notablythe French organisations INSERM(Institut National de la Santé et dela Recherche Médicale) and CNRS(Centre National de la RechercheScientifique)) have become moreactive in the field.Of the major pharmaceutical

companies, only Roche, Novartis andBayer are among the top 10

applicants. Blockbuster drugs – oftenconsidered the “Holy Grail” of thepharmaceutical industry – are aconcept contrary to personalisedmedicine, so this is not whollysurprising. Indeed, annual applicationnumbers from private businessesamong the top 22 filers dropped 43%between 2006 and 2011.In terms of geographical filing

trends, more individual patentapplications were made in the US(8382) than in any other jurisdiction,followed by Europe (4383), Japan(2606), Canada (2359) and Australia(2335). Newer markets, such as Chinaand South Korea, show low numbersof filings and, of those applicationsfiled in China, the vast majority arefrom domestic companies. Foreignorganisations are clearly yet toconsider China a key geography forpersonalised medicine.At this point, it is perhaps worth

making a note on legaldevelopments within the area ofpatent eligibility. In recent years,patents claiming gene sequenceshave led to significant debate andthe development of new legaldoctrine. Most notably, the US hasconsidered this at some length,causing great concern for theindustry. Following the widely-reported Myriad case, the UnitedStates Patent and Trademark Office(USPTO) issued new guidelines1,2 fordetermining the patentability ofclaims which involve laws of nature,natural phenomena or natural

products. Product claims are onlyallowable if there is a “markeddifference” in structure between theclaimed product and a productoccurring in nature. Most crucially,the guidelines extend the Court’sruling in Myriad to all naturalproducts. As such, medicinalformulations containing naturallyoccurring agents, such as antibiotics,antibodies or peptides, all of whichhave traditionally been patentable,may become more difficult toprotect. Unsurprisingly, concernshave been raised over the apparentchange in the law, but it remains tobe seen whether the courtsthemselves will adopt a similarposition to the USPTO. In themeantime, the increased burden inobtaining and defending patentrights may have a negative impacton patent filings in the US,particularly from public entities.The USPTO’s stance on the

patentability of natural products isnot followed in other jurisdictions,although territories, such as Europe,impose other restrictions on thepatentability of, for example, stemcells3 and methods of treatmentand diagnosis.

Synthetic biologySynthetic biology refers to theengineering and manipulation ofexisting biological systems and thecreation of new systems for variouspurposes. Currently, the maincommercial application of synthetic

Table 1: Top filers inpersonalised medicinebetween 2003 and 2013

Organisation Patents*

1 NIH 304

2 Roche 127

3 University of California 85

4 INSERM 80

5 Johns Hopkins University 81

6 Novartis 72

7 US Department of Health 68

8 Oncotherapy Science 61

9 University of Southern California 46

10 Bayer 45

=11 Mayo Foundation 44

=11 Siemens Healthcare 44

13 Amgen 40

14 University of Texas 39

15 Epigenomics 37

16 Merck 36

17 Dana Farber Cancer Institute 35

=18 CNRS 31

=18 Janssen Diagnostics 31

=18 Stanford University 31

=21 Ohio State University 30

=21 GlaxoSmithKline 30

* Patent applications since 2003, one entryper patent family. Data for 2012 and 2013incomplete due to an 18-month delay inpublication after filing.

Myriad versus Association for Molecular PathologyIn June 2013, the US Supreme Court handed down its ruling in this high-profile case,which sought to establish if Myriad’s patents on the BRCA1 and BRCA2 genes, whichincrease susceptibility to breast cancer, were valid. The Court ruled that inventionsderiving from isolated human DNA cannot be patented and that Myriad’s patentswere, therefore, invalid. This ruling, together with the 2012 Mayo versus Prometheusruling, was later applied by USPTO in its ‘Guidance For Determining Subject MatterEligibility of Claims Reciting or Involving Laws of Nature, Natural Phenomena, &Natural Products’.

Mayo versus PrometheusIn March 2012, the US Supreme Court handed down its much-anticipated decision,relating to the patentability in the fields of diagnostic testing, personalised medicineand biotechnology. The judgment held that that the claims in Prometheus’ patents,which were directed to methods for optimising the efficacy of a drug, were directedto laws of nature and, consequently, not patentable.



biology is in the biofuels space, butother uses in pharmaceuticals,materials science and biosensingtechnology are perhaps not far off.At first glance, the figures for

patent applications in this areaappear dramatically different fromthe other sectors analysed in thereport, with the RussianGovernment topping the list ofapplicants and the RussianDepartment of Science and theRussian Department of HigherEducation and Research followingclosely behind (see Table 2).Similarly, Chinese universities andinstitutions are heavily representedin the rankings. However, theseentities do not tend to file widelyoutside their home country. Thisstrongly suggests reasons for filingother than to simply protect the

technology. The only Europeanorganisation among the top filers isCNRS (12th place).The main split in the data seems

to be the distinction betweenprivate corporations and publicbodies. By far the majority ofapplications are made in the nameof public bodies. Privateorganisations file relatively fewapplications, representing onlythree of the top 21 filers and onlytwo patents have been filed bypharmaceutical companies Bristol-Myers Squibb and Merck since2007. This may indicate that thetechnology is still at a relativelyearly stage, coming primarily fromresearch institutes and universities.Even with the Russian and

Chinese data included, the US is themajor target for patentees, with atotal of 3360 applications filed theresince 2003. A key difference to othertechnologies, however, is that Chinacomes second with 1545applications. This may be inflated bythe number of applications filed inChina only, but it may also representChinese investment in the field.

Sequencing technologySince discovering the double helix,scientists have been driven by aninsatiable desire to decode andunderstand the complex chemicalsignatures of the genome. As partof this, the technology used tosequence nucleic acids has seenrapid development in recent yearsand now finds application not onlyas a standard research tool but inpersonalised medicine, forensicscience and agriculture.Unlike the other areas of

technology we analysed, privatecompanies represent the leadingpatent applicants (see Table 3). Thetwo largest players in the field ofsequencing technology are Illuminaand Life Technologies (now ThermoFisher Scientific). Although publicresearch institutes and universitiesdo not figure heavily among the topapplicants, the NIH and HarvardUniversity are the largest of thistype of filer.One interesting observation is the

emergence of smaller companies

with disruptive technologies. Forexample, Oxford NanoporeTechnologies’ innovative nanopore-based sequencing methods are thesubject of a number of patentapplications, the earliest of whichwere filed in 2009/10.The data also highlights the

emergence of Chinese companyBGI Shenzhen (BGI) as a major forcein the sequencing field since 2007/8.BGI technology is spread over awide area covering methods andconsumables for use in sequencing.In terms of the key territories for

total patent applications filed, theUS is a long way in front with a totalof 2871 publications since 2003.However, Europe and Japan featurestrongly too with 739 and 520publications, respectively. China isyet to match these territories, butsince BGI have only recently risen toprominence, this is perhaps notsurprising.

DiscussionAs the medical applications ofgenome research become clearer

Table 2: Top filers in syntheticbiology between 2003 and2013


1 Russian Government 49

2 NIH 33

3 Russian Department of Science 28

4 University of California 27

5 Bristol-Myers Squibb 25

6 Russian Department of Higher Education and Research 24

7 Nanjing University 23

8 Zhejiang University 21

=9 Riken 20

=9 University of Jiangnan 20

11 Tsinghua University 17

12 CNRS 15

=13 Japanese Science and Technology Agency 13

=13 Kyoto University 13

=15 Chongqing University 11

=15 Corning 11

=15 US Department of Defense 11

=15 US Department of Energy 11

=19 Beijing University of Science and Technology 10

=19 Merck 10

=19 National Science Foundation 10

Table 3: Top filers insequencing technologybetween 2003 and 2013


1 Illumina 80

2 Life Technologies 70

3 Pacific Biosciences 35

4 Roche 24

5 NIH 23

=6 Harvard University 20

=6 Intel 20

=6 BGI Shenzhen 20

9 Abbott 17

=10 University of California 15

=10 Columbia University 15

=12 Hitachi 13

=12 Stanford University 13

=14 Agilent Technologies 12

=14 Oxford NanoporeTechnologies 12

=16 Helicos BioSciences 10

=16 Keygene 10

=16 Sequenom 10

and we enter an age ofpersonalised medicine, theprotection of intellectual propertybecomes increasingly important.While big pharma companies havenot shown the same enthusiasm aspublic bodies for personalisedmedicine, we may well start to seean increase in filings coming fromthese types of company; but theywill have to catch up and may haveto rely on licensing models for manyyears before entering the market ontheir own terms. However, we must not forget the

new USPTO guidelines issued in thewake of the Myriad/Prometheusdecisions. Unless these are revised,they could have a disastrous effecton patent applications in thepersonalised medicine area, leavingcompanies unable or unwilling tocommercialise their research.The sequencing technology

market appears to have maturedand companies with disruptivetechnologies are appearing amongthe top filers. We are also seeinginterest from emerging markets likeChina – where life sciencescompanies have, for many years,lagged behind their electronicscounterparts in terms of patentfilings around the world.

Synthetic biology is the leastestablished of the technologies wehave analysed, with patent filingfigures easily skewed by localconsiderations. Private companiesare clearly yet to make up theirminds on the benefits of researchinto this area with vacillating interestfrom both pharmaceutical andindustrial companies in the area.

References1 United States Patent and TrademarkOffice. Guidance For DeterminingSubject Matter Eligibility Of ClaimsReciting Or Involving Laws of Nature,Natural Phenomena, & Natural Products.Alexandria, VA: USPTO; 4 March 2014.http://www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf

2 United States Patent and TrademarkOffice. Evaluating Subject MatterEligibility Under 35 USC § 101: March2014 Update. Alexandria, VA: USPTO;19 March 2014.http://www.uspto.gov/patents/law/exam/myriad-mayo_slides_20140319.pdf

3 Court of Justice of the European Union.Press Release No 112/11. Judgment inCase C-34/10 Oliver Brüstle vGreenpeace e.V. A process whichinvolves removal of a stem cell from ahuman embryo at the blastocyst stage,entailing the destruction of that embryo,cannot be patented. Luxembourg: Curia,18 October 2011.http://curia.europa.eu/jcms/upload/docs/application/pdf/2011-10/cp110112en.pdf



consider the CJEU’s new test andprovide further guidance.References seeking further clarityremain likely.In Lilly, the CJEU also made

comments considering whetherthe patentee’s level ofinvolvement in the developmentof a product granted an MA onthe basis of a functionalspecification was relevant to thegrant of an SPC. The UK Judgenoted the comments andconsidered them to relate to anargument as to the party entitledto any SPC granted; an argumentno longer being pursued in thiscase. That issue is for another day.

References1 C-484/12, ECLI:EU:C:2013:828.2 C-443/12, ECLI:EU:C:2013:833.3 C-493/12, ECLI:EU:C:2013:835.4 C-322/10 ECLI:EU:C:2011:773.5 C‑181/95 ECLI:EU:C:1997:32.6 C-322/10, ECLI:EU:C:2011:773.7 Daiichi, C-6/11, ECLI:EU:C:2011:781.

SUPPLEMENTARYPROTECTION CERTIFICATES:OF CLARITY ANDCONFUSIONContinued from page 5

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Readers will have enjoyed MichaelAnisfeld’s humorous polemicentitled ‘Unstandard Standards’ inthe March 2014 issue of IndustrialPharmacy. This argued the case fora single worldwide pharmacopoeia.There is a cogent case to be madefor increasing the speed and extentof pharmacopoeial harmonisation.Sadly, however, Mr. Anisfeld's articlegave a rather selective and flawedanalysis of the history and progressof pharmacopoeial harmonisation.This article is written to providereaders with a more completereview.

The earliest attempts tosystematise knowledge about drugsand their preparations were theformularies, such as those producedby Dioscorides (c.40–90 AD) ‘Demateria medica’ and by Galen(129–c.210 AD) ‘On the Power ofSimple Drugs’. The first officialpharmacopoeias were produced byindividual physicians or groups ofphysicians for use in their own citiesor city-states. The official guide forthe apothecaries of Florence wasthe ‘Nuovo receptario…’ publishedin 1498. Other cities such asBarcelona, Saragossa and

Nuremberg followed. The first useof the word ‘pharmacopoeia’ was in1548 with the publication by theFrench physician Jacques du Bois ofhis ‘Pharmacopoea, libri tres’. The first truly national

pharmacopoeia was the LondonPharmacopoeia published by theRoyal College of Physicians in 1618and official in England. In 1754, theCollege of Physicians in Dublinadopted the text as official inIreland. Ten editions werepublished, the last in 1851. The firstedition of the EdinburghPharmacopoeia was in 1699 and thelast in 1841. The first edition of theDublin Pharmacopoeia was in 1806and the last in 1850. The EdinburghPharmacopoeia was the basis of thePharmacopeia of the MassachusettsMedical Society in Boston in 1809.Since more than 90% of the articlesin the 1820 first edition of theUnited States Pharmacopeia (USP)derived from the MassachusettsPharmacopeia, the EdinburghPharmacopoeia provided much ofthe content of the first USP.The first edition of the British

Pharmacopoeia (BP) was publishedin 1864 and this was the firstinternationally harmonisedpharmacopoeia. It superseded thethree national Pharmacopoeias ofLondon, Edinburgh and Dublin. ThePreface to this edition stated that itreconciled ‘the varying usages, inpharmacy and prescriptions, of thepeople of three countries hitherto inthese respects separate andindependent…’ Indeed, 2014 isbeing celebrated as the

PHARMACOPOEIALHARMONISATION: ANHISTORICAL PERSPECTIVEby Tony Cartwright

Michael Anisfeld’s article in the March issue arguingthe case for a single worldwide pharmacopoeia

ignores the very considerable progress already made ininternational harmonisation of standards.Pharmacopoeial harmonisation has been a continuousprocess since 1864 when the British Pharmacopoeiasuperseded the national pharmacopoeias of London,Edinburgh and Dublin. Achievements includeharmonisation of the strengths of materia medica byInternational Agreements in 1902 and 1930,establishment of international biological standards in1924, and a system of International NonproprietaryNames in the 1950s. The standards of the EuropeanPharmacopoeia are now official in 38 countries. Althoughthe pace of harmonisation through the PharmacopoeialDiscussion Group is slow, real progress has beenachieved. The future lies in enhanced cooperation andwork-sharing between the national and regionalpharmacopoeias rather than a new GlobalPharmacopoeia.

Tony Cartwright is a retired pharmaceutical regulatory consultant. He worked with theBritish Pharmacopoeia Commission and the UK Medicines Control Agency in a varietyof roles before joining a Contract Research Organisation. He was the first Chairman ofthe Quality Working Party for the European Committee for Proprietary MedicinalProducts, and chaired some of the early International Conference on Harmonizationtopic discussions on quality topics. He is now an occasional consultant and writer. Hehas just written a book entitled The British Pharmacopoeia, 1864 to 2014: Medicines,International Standards and the State.


PHARMACOPOEIAL HARMONISATION: AN HISTORICAL PERSPECTIVE continued

sesquicentenary (150th birthday) ofthe first publication of the BP. Theearly editions were official in theBritish Empire and all of the BritishDominions in North America, Africa,Asia, the West Indies, India andAustralasia. The BP is still widelyused in over 100 countries.Many of materia medica in the

early national pharmacopoeias wereherbal preparations which couldvary in strength. Nineteenth centurytravellers were exposed to thehazard of what purported to be thesame material having differentstrengths in different countries. In1902, an International Conferencewas held in Brussels for Unificationof the Formulae for Potent Drugsand Preparations in several of thenational pharmacopoeias. This ledto the adoption of a series ofrecommendations in the form of anInternational Agreement. In 1930, afurther International Agreementbecame operative and this wasapplied in the 1932 BP. Forexample, Tincture of Digitalis wasstandardised at 10 per cent byweight and Opium Powder at 10per cent of anhydrous morphine. In 1924, the Health Committee of

the League of Nations set up afterWorld War I established aPermanent Commission onBiological Standardisation and theirstandards were used in carrying outthe biological assays in the 1932 BP,such as the test for potency ofDigitalis. The PermanentCommission held sessions in 1926,1928, 1930, 1931 and 1934. An inter-governmental conference was heldin Geneva in 1935 recommendingthat a Permanent Commission onBiological Standardisation wouldadopt international standards to beused in all countries. These weredistributed by the Danish StateSerum Institute and the NationalInstitute of Medical Research inLondon. In the 1970s, theresponsibility for provision ofbiological standards in the UK wastransferred to the National Institutefor Biological Standards andControl (NIBSC), which is now partof the Medicines and HealthcareProducts Regulatory Agency. NIBSC

is the main custodian of biologicalreference materials for World HealthOrganization (WHO) together withother custodian laboratories in theAnti-Viral Research Branch of theNational Institute of Allergy andInfectious Diseases (NIAID) and theCenters for Disease Control andPrevention in the USA, at theEuropean Directorate for theQuality of Medicines andHealthcare (EDQM), the Paul EhrlichInstitute in Germany and theUniversity of Washington in Seattle,USA. These biological standards areused in pharmacopoeial testsspecified in the majorpharmacopoeias.In 1937, the Health Organization

of the League of Nations set up aTechnical Committee ofPharmacopoeial Experts to startwork on the InternationalPharmacopoeia. The first meetingwas held in May 1938 and thesecond in Geneva in 1939. The workwas interrupted by World War II. In1947, the WHO decided to set upan Expert Committee on Unificationof Pharmacopoeias. The first editionof the International Pharmacopoeiawas published in two volumes in1951 and 1955. In 1975, it wasdecided that the main purpose ofthe International Pharmacopoeiawould be to serve the needs of thedeveloping world and, in particular,to provide monographs for drugson the Essential Drugs List andthose important to the WHOprogrammes. Thus, the latestedition includes monographs onantimalarial drugs, antiretroviraldrugs and combination products fortreatment of tuberculosis.When the modern synthetic

chemical drugs were marketed inthe 20th century, theirmanufacturers sold the productsunder a trade name. Thepharmacopoeias then sought todevise a simple non-proprietaryname which could be used as thetitle of the drug substancemonograph instead of thecomplicated systematic chemicalname – the generic name. Manycountries adopted their ownnational lists of non-proprietary

names – such as the BritishApproved Names and the UnitedStates Approved Names (USANs).During World War II, the BPCommission issued new approvednames for drugs that were nowmanufactured in Britain but hadpreviously been imported fromGermany. In 1953, the WHOinstituted a formal system forestablishment of InternationalNonproprietary Names (INNs). Thisprocedure has now been updated anumber of times. The use of INNs ismandatory in the European Unionunder Directive 2001/83/EC;however, some older nationalnames may still be used elsewhere.Thus, Paracetamol is the INN andAcetaminophen used in the US is aUSAN.The European Pharmacopoeia

(Ph. Eur.) is an example ofpharmacopoeial harmonisationwhich already encompasses manycountries. It was established in 1964with eight countries originallyparticipating, and now has 38signatories to the PharmacopoeiaConvention and 18 other countries(including the USA and the RussianFederation) participating asobservers at the meetings of theEuropean PharmacopoeiaCommission. The first volume of thePh. Eur. was published in 1969. Thelatest edition is the eighth whichwas published in July 2013. The Ph.Eur. includes general monographsfor drug products, drug substancesand excipients and these are officialin all of the 38 signatory countries,which include all of the EuropeanUnion countries. NationalPharmacopoeias can translate andreprint the text and monographs.Thus, for example, the text of theBP includes all of the generalmethods and monographs from thePh. Eur. However, the BP alsoincludes monographs for all of themajor pharmaceutical medicinalproducts prescribed in the UK, so ismuch more than a ‘clone of the Ph.Eur.’ that Mr. Anisfeld mentions.As Mr. Anisfeld described, the

tripartite PharmacopoeialDiscussion Group (PDG) consistingof representatives from the USP, the

PHARMACOPOEIAL HARMONISATION: AN HISTORICAL PERSPECTIVE continued


Ph. Eur. and the JapanesePharmacopoeia was established in1989. It meets to consider proposalsmade by national associations ofmanufacturers of pharmaceuticalproducts and excipients for thework programme. Its programme ofharmonisation includes general testmethods, General Chapters,methods for biotechnologyproducts and excipientmonographs. Currently, 29 of the 35General Chapters and 46 of the 62excipient monographs in itsprogramme have been harmonised.Although the harmonised excipientmonographs comprise only a smallproportion of those used, they areamongst the most frequently usedby manufacturers in their products.The PDG is looking at ways toimprove the speed and extent ofharmonisation and this is to bewelcomed.Collaboration and cooperation

between the pharmacopoeias hasbeen practised for many years.Thus, the BP and USP havecollaborated almost from thebeginning exchanging information,copies of new editions and withvisits by senior staff. In 2004, theInternational Conference of DrugRegulatory Authorities discussedthe idea of a worldwide approachto setting pharmacopoeialspecifications. This led WHO toorganise a series of InternationalMeetings of WorldPharmacopoeias. A guideline onGood Pharmacopoeial Practice isbeing developed. Work-sharing andmutual acceptance of monographs

was also discussed.Mr. Anisfeld quotes two examples

of possible difficulties in achievingharmonised standards. The firstexample is that of ParacetamolTablets in the US and UK havingdifferent dosages, implying a lack ofharmonised drug standards.However, his article confuses theusual strength of the commercialtablet preparations available in thetwo markets (325mg in the US and500mg in the UK) with therecommended dosage of the drug.He asks ‘surely British headachesare not more severe than Americanheadaches requiring higherdosages of the same drug…’ Infact, the recommended adult dosesof paracetamol for treatments ofpain and fever in the two countriesare nearly identical. The second example relates to

the difficulty in identifying safedrugs to include in apharmacopoeia, and Mr. Anisfeldsuggests aspirin as such anexample. He asserts that aspirin wasknown for hundreds of years as afolk-medicine. The activeconstituent in willow bark is salicylicacid not aspirin, and it was morethan just a folk-medicine as it wasthe subject of one of the firstreported clinical trials by theReverend Edward Stone in 1763.The first synthesis of aspirin was byCharles Gerhardt in 1853. In 1897,Felix Hoffman improved thesynthesis and made it into acommercial process which Bayercould then use to market the drug.Mr. Anisfeld suggests that safety

issues now known about aspirinwould have prevented its approvalby today’s regulatory agencies.However, the agencies do not justlook at safety per se. They nowreview the risk/benefit and theundoubted benefits of aspirin for avariety of indications would mean itwould be approved. Aspirin was thesecond most commonly prescribeddrug in the community in Englandin 2013.Mr. Anisfeld also argues that his

single worldwide pharmacopoeiawould produce considerablesavings in cost and manpower asthere would be no need to have thestaff of national and regionalpharmacopoeias. His analysisallocates all of the costs of the USPConvention and the EDQM to theUSP and Ph. Eur. However, the USPproduces a number of othercompendia and the EDQM also hasmany other responsibilities. Mr. Anisfeld does not tell us what

would be included in his singleworldwide pharmacopoeia –whether it would include tropicalmedicines, herbal medicines,Ayurvedic medicines andhomeopathic medicines. Thenational and regionalpharmacopoeias can respond tolocal needs and the practices ofmedicine and pharmacy, and caninclude indigenous medicines aswell as modern synthetic chemicaland biological drugs. The futuresurely lies in enhanced cooperationand work-sharing, rather thaninventing a new GlobalPharmacopoeia.

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A unique and comprehensive guide to ensureregulatory compliance and success inpharmaceutical regulatoryinspections

Edited by Madhu Raju SagheeQuality Assurance, Micro Labs, and Director of PHSS, India

Foreword by Peter D. SmithVice President, Strategic Compliance,PAREXEL Consulting, USA

Foreword– Peter D. Smith

Preface– Madhu Raju Saghee

1 Basic Concepts of Global GMPRequirementsby Tim Sandle and Madhu RajuSaghee

2 FDA Drug Regulation andEnforcementby Seth Mailhot

3 System Based Approach toInspectionsby David Barr and Tim Sandle

4 Preparing for PreapprovalInspectionsby Ron Johnson

5 Effectively Managing and SurvivingFDA Inspectionsby John Avellanet

6 Guide for Successful EUInspection Managementby Siegfried Schmitt and Nabila Nazir

7 Regulatory Requirements ofJapanese GMP Inspectionsby Yoshikazu Hayashi

8 Preparing and Management ofInternational Inspectionsby Andreas Brutsche and Tim Sandle

9 Handling and Responding to PostInspectional Observationsby Tim Sandle, Madhu Raju Sagheeand David Barr

10 Preparing for RegulatoryInspections of Sterile Facilities:The Focal Pointsby Tim Sandle

11 Preparing for RegulatoryInspections of API Facilities: TheFocal Pointsby Siegfried Schmitt and RichardEinig

12 Optimizing your RegulatoryComplianceby Mark Tucker

PHARMACEUTICAL

REGULATORY

INSPECTIONS

“EVERY INSPECTION A SUCCESS STORY –

A PRACTICAL GUIDE TO MAKE IT HAPPEN"

EDITED BY MADHU RAJU SAGHEE

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

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

In over 500 pages and twelve chapters thisunique book provides a focussed account ofregulatory issues from pre-approvalinspections and the inspection itself to post-inspection and maintaining compliance. This isa book that every pharmaceutical company willwish to study before and during any inspectionprocess to ensure a successful outcome.

Complete Remit

The book is a fully detailed and practical guidecontaining advice and insight to help anypharmaceutical organisation prepare for GMPInspections, understand key regulatory issuesand review inspectorate trends and findings.

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The authors, with a wealth of regulatoryexperience behind them, express their viewsand provide useful and practical tips forsucceeding in vital regulatory inspections

International Applications

The book includes chapters covering FDAInspections, EU Inspections, JapaneseInspection and International Inspectionprocesses.


EIPG affiliation forprofessional developmentavailable fromPharmaConsult Global Ltd.

The second report on the 2009 recommendationon Patient Safety and Quality of Care (Citizen’sCharter) report 2009/151/01, published last month,has, in the last year, resulted in major changes tomany EMA regulations.

All professionals working in the supply ofmedicines should familiarise themselves with thecontent of these amended regulations since theybring with them additional legal responsibilitiesand accountabilities which form an essential partof all continued professional developmentprogrammes.

A wide range of e-Learning modules explainingthe changes are available online fromPharmaConsult Global Ltd and are offered to theindustrial pharmacist members of professionalassociations affiliated to EIPG. Prospectiveregistrants can review details of the course byclicking on “Details” (next to “Buy now”) and“View Detailed Description” where the coursedescription and short demo of the e-Learningmodule is available.

PharmaConsult Global e-Learning modulescomprise of a presentation, reading material, adelegate assessment questionnaire, andcompletion. Each month, we will feature two ofthe e-Learning courses and will also provide awebinar which will allow the delegate to discussthe impact of the new regulation with internationalsubject experts and peers to get a detailedunderstanding of the course.

The PROPOSED programme of e-Learning and subject expert discussiongroups available from September 2014

September 2014: Biotechnology andBiosimilars

This course provides an introduction to theinternational GMP standards required to supportmanufacturing and inspection activities ofbiotech manufacturing facilities and drug

products, and the EMA Guideline on SimilarBiological Medicinal Products ContainingBiotechnology-derived Proteins as ActiveSubstance.

The webinar will consider the original datarequired to register a biosimilar product and anyother topic introduced into the interactivediscussion.

October 2014: Product Development

This module is an introduction to internationalregulatory requirements for training staff workingin product development, manufacturing anddistribution with the basis of the knowledgeessential for obtaining a marketing authorisationfor a new product.

The webinar will consider case studies for thedevelopment of different dosage forms, and theregulatory priorities considered essential indifferent regions.

October 2014: Pharmaceutical QualityManagement Systems

This course will examine the application of the ICHstandards Q9 Quality Risk Management, Q10Pharmaceutical Quality Systems, and Q11Development and Manufacture of API, for thestandard pharmaceutical processes required byregulatory authorities in the US and Europe, andthe additional legal responsibilities of keymanagement.

The webinar will review the requirements forpharmaceutical quality management systems inproduct development, clinical trials, APImanufacture, product manufacture and productdistribution.

November 2014: Medical Devices

This module will provide an overview of thecurrent medical device requirements and data


expected by the FDA and EMA to achieve amarketing authorisation.

The webinar will consider the impact onregistration by adding an active ingredient incombination with the medical device.

November 2014: GMP Manufacturing

This course will introduce the historicalbackground to the GMPs to provide thenecessary understanding regarding theregulatory authorities’ concerns with respect toproduct protection. It will discuss the movementtowards harmonising the GMPs in the world’sregulatory markets by discussing the GMPs fromthe US and Europe. ICH Q7 will be discussed asa general set of agreed requirements and, finally,findings from recent FDA inspections will bepresented as we understand the reasons forGMPs in such a way as to provide a necessaryunderstanding of why we do what we do.

The webinar will discuss the impact of thechanges made to Volume 4 Good ManufacturingPractice (GMP) Guidelines in the last 12 months

December 2014: Pharmacovigilance

The course will review good pharmacovigilancepractices and the set of measures in theGuidelines on Pharmacovigilance (Volume 9BOctober 2011) and Good Vigilance Practice(published February 2014) drawn up to facilitatethe performance of pharmacovigilance in the EU.

The webinar will consider the requirements forbecoming a qualified person responsible forpharmacovigilance.

January 2015: GMP Manufacturing

This course will discuss the reasons for GMP, evaluatethe background and drivers for GMP both in the USand Europe, and evaluate inspection findings frommanufacturing sites from around the world.

The webinar will consider the impact ofintroducing changes to Volume 4 GoodManufacturing Practice (GMP) Guidelines.

January 2015: Regulatory Affairs

This module provides an introduction tointernational regulatory requirements in productdevelopment, manufacturing and distribution forall staff working in health care and thepharmaceutical industry.

The webinar will review the issues arising fromdiscontinuing use of NeeS to present data forproduct registration in the different memberstates of Europe.

February 2015: Clinical Research

This is a practice course designed for sponsorsand investigators, as well as their research staffmembers, and includes the most common rules toavoid non-compliance, known as “The 12 rules”.

The webinar will discuss introduction of therequirements of the EU regulation 536/2014 in toclinical trials practice and the differences inrequirements from the Directive 2002.

March 2015: Good Distribution Practice

This course will review the NEW Good DistributionPractice of Medical Products Guidelines 2013 343-10 and the Falsified Medicines Directive 2011/62which came into effect in many European statesfrom January 2013.

The webinar will discuss the benefit thatintroduction of pack serialisation will have on thedistribution of pharmaceutical products

The topics for discussion in all of the webinarsmay be changed if there are different issuesidentified by delegates for discussion.


regulatory reviewWorryingly, during the periodcovered, it should be noted that,again, there were incidents oflack of sterility assurance onproducts from two differentcompounding pharmacies in theUSA. Also an outbreak of bloodpoisoning (septicaemia)occurred in England fromBacillus cereus infection. Thesource was probablycontamination of a single day’sproduction of intravenous liquidproducts (total parentalnutrition). There was also amulti-batch product recall in theUK following the potential forchemical contamination ofproduct which was discoveredduring an Medicines andHealthcare Products RegulatoryAgency (MHRA) inspection.

USAThe Food and Drug Administration(FDA) has issued the followingGuidances/draft Guidances forIndustry.

Immunogenicity Assessmentfor Therapeutic ProteinProducts This outlines and recommendsadoption of a risk-based approachto evaluating and mitigatingimmune responses or adverseimmunologically related responsesassociated with therapeutic proteinproducts.

Reference Product Exclusivityfor Biological Products FiledUnder Section 351(a) of thePublic Health Service Act This assists developers, sponsors ofbiologics license applications, andother interested parties in providinginformation that will help FDAdetermine the date of first licensurefor a reference product.

Neglected Tropical Diseases(NTD) of the Developing WorldThis will assist sponsors with littleexperience in working with the FDA.It addresses FDA’s current thinkingregarding the overall drugdevelopment program for thetreatment or prevention of NTDs,

including clinical trial designs andinternal review standards to supportapproval of drugs.

Compounding OutsourcingFacilities Under Section 503Bof the Food, Drug & Cosmetic(FD&C) Act This interim guidance reflectsFDA’s intent to recognise thedifferences between compoundingoutsourcing facilities andconventional drug manufacturers,and tailors current goodmanufacturing practice (CGMP)requirements to the nature of thespecific compounding operationsconducted by outsourcing facilitieswhile maintaining the minimumstandards necessary to protectpatients from the risks ofcontaminated or substandardcompounded drug products. FDAwill focus its inspectional andenforcement efforts on thoseaspects and such operations thatpose the highest risk to patientsafety, in particular, sterilityassurance, safety, subpotency,superpotency, and labelling ordrug product mix-ups.

Pharmacy Compounding ofHuman Drug Products UnderSection 503A of the FD&C Act This announces FDA’s intention toregulate/use enforcement on suchestablishments now that section503A has been amended byCongress to remove the advertisingand solicitation provisions that wereheld unconstitutional by the USSupreme Court in 2002.

Drug Supply Chain SecurityAct: Identification of SuspectProduct and Notification This is intended to aid tradingpartners in identifying a suspectproduct and terminatingnotifications regarding illegitimateproduct.

Expedited Programs for SeriousConditions – Drugs and BiologicsThis provides a single resource forinformation on expedited programsfor serious conditions e.g.: fast track

designation/breakthrough therapydesignation/accelerated approval,and priority review designation.

EuropeStrategy for elementalimpurities and upcomingInternational Conference onHarmonisation (ICH) Q3DguidelineA strategy for the revision ofEuropean Pharmacopoeia (Ph.Eur.)texts concerned has been drawn upto ensure a consistent approachbetween licensing authorities andthe Ph.Eur.

Ph.Eur. first draft finishedproduct monograph withchemically defined activesubstance The Ph.Eur. Commission has startedworking with these monographs.The first such draft monograph hasnow been published for comments.This expands the scope of the Ph.Eur. The monographs will follow thesame general principles as for othermonographs.

Use of a Certificate ofSuitability (CEP) for a startingmaterial in an application fora CEPA document is now available fromthe European Directorate of theQuality of Medicines to provideclarification on this issue.

Qualified person (QP)declaration re GMPcompliance of activesubstance manufactureThe European Medicines Agencyhas released the final version of theQP Template and the relatedGuidance document.

MHRAMHRA position on freightconsolidation depots (freightforwarders) Since the application of the FalsifiedMedicines Directive (FMD), bothexport and holding of humanmedicines for export requiresauthorisation. Some companies/sitesnot previously regulated now


require a wholesale distributionauthorisation (WDA(H)). Gooddistribution practice (GDP)inspectorate has also issuedguidance on short-term storage ofambient and refrigerated medicinalproducts, confirming situationsrequiring a WDA.

MHRA updated GuidanceNotes 5 and 6 These updates outline the keyobligations for maintaining thelicence/registration and will helpapplicants and those who hold amanufacturer’s licence, wholesaledealer’s licence or broker registration.

Consultation (MLX387) safetyfeature: 'black' and 'white' lists The FMD has introduced obligatory‘safety features’ to verify theauthenticity of medicinal products.• All prescription medicines willbear the safety features unlesslisted by the EuropeanCommission.

• All non-prescription medicines willnot bear the safety features unlesslisted.

MHRA seeks views on products thatshould be listed.

Generic Medicine QualityForumMHRA co-hosted the first meetingof a new forum focused on ensuringthe manufacturing quality of genericmedicines in the UK.

InternationalICHAssessment and control ofDNA reactive (mutagenic)impurities in pharmaceuticalsto limit potential carcinogenicrisk (M7)This guideline emphasises bothsafety and quality risk managementin establishing levels of mutagenicimpurities that are expected to posenegligible carcinogenic risk. Itoutlines recommendations forassessment and control ofmutagenic impurities that reside orare reasonably expected to reside infinal drug substance or product,taking into consideration theintended conditions of human use.Implementation of M7 is

encouraged after publication;however, because of the complexityof the guideline, application of M7 isnot expected (with certainexceptions) prior to 18 months afterICH publication.

IndiaTrack and trace requirementsdelayed for primarypackaging of exportedproductIndia has deferred the requirementof affixing barcodes on primary levelpackaging until a new date isnotified. However, the requirementto affix bar codes on tertiary andsecondary level packaging, whichhave already been implemented,continue to be in force.

For further information on these andother topics we suggest you refer to thewebsites of relevant regulatory bodiesand to current and past editions of “GMPReview News” published by EuromedCommunications. To subscribe to thismonthly news service [email protected]

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Clinical Research Manual Editors: David Luscombe and Peter D Stonier20 Chapters over 600+ pages £190.00

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REGULATORY REVIEW continued


Mother lodeNHS data held by hospitals and GPpractices are not combined.Combining, according to ProfessorSir John Savill, Head of the MedicalResearch Council, “could turn theUK into the best clinical lab in theworld and the benefit would be feltfirst in the UK”. Once all this isexplained properly, Sir John thinksthe public will accept this as a “nobrainer”. Governmental decisionmay be about now. The long-established, large British NHSholds gargantuan information: amother lode. Patient data types aregreen: anonymous; amber:“pseudonymised” by removingidentifiers, such as name andpostcode; and red: identifiespatient.

What we could achieve Combined NHS retrospective data,including patients’ geneticbackgrounds, diagnoses, drugs, andoutcomes, could permit mining forpatterns. For example, the mosteffective drugs for patients withspecific genetic natures mightemerge. One illustration is that, for breast

cancer, the “FEC” (fluorouracil,epirubicin and cyclophosphamide)regime may “achieve” excellentresults in one patient but be lessefficacious in another. This may beassociated with the varying geneticnature of those two patients. Thiswould supplement in vitro researchinto cancer cell lines of varyinggenetics that recently resulted in achemotherapy/cancer“encyclopaedia”. The buzz phraseis “personalised medicine”; buzz

word: “tailored”. Such medicine output could

rocket; a revolution aided by theNHS working in concert with thepharmaceutical industry. It is keento play its part in finding the bestdrugs for specific jobs: tomorrow’s“magic bullets”, contributing itsexpertise in toxicology,pharmacology, statistics and so on.Modern statistics, probing

investigational design, computerprograms, collaborative yet cannyindustrial eyes and the gargantuandata from a properly joined-up NHScould mine that precious motherlode.

Concerns aboutconfidentialityBut it may be aborted because ofconcerns about patientconfidentiality from “consentfetishists” (to quote Sir John). Theyare concerned that “amber data”may result in identification ofindividuals. That risk does exist.Amber data could tie, with areasonable degree of certainty, asmall minority of patients’ geneticsto the outcome of their treatmentwith a specific drug. The patient-identifying

unambiguous “red data” appearsnot on offer to the pharmaceuticalindustry. I wonder why. I speculatethat, generally, the public only hearabout the pharmaceutical industrywhen something goes wrong; thinkDevonport incident, Thalidomide,TGN1412. Bad press includescarelessness, only interested inprofit; one sideline is bribery.I would not wish to include

sharing of red data with insurancecompanies. But I do ask, “Why not

share red data with thepharmaceutical industry?”Individual companies alreadypossess it for their specific clinicaltrials. Pharmaceutical industry staffinclude professionals, such aschartered scientists, medicalpractitioners and pharmacists(bound by their ethical codes andliable to be struck off), and otherswho have signed confidentialityagreements. Comparatively“junior” “lay” administrative staff,who have signed confidentialityagreements, in British GP surgeriesand hospitals, routinely accesspatients’ red health data andrespect their confidentiality.Certainly, risks exist. Broachesoccur; individuals and systems havesuboptimalities. Governmentorganisations are less-than-perfect.One illustration is the loss ofmillions of records of personal datafrom the UK Department of Workand Pensions in 2008. By the way,your kindly superstore, helped bytheir loyalty card scheme, fromchanges in the pattern of yourpurchasing, may well know beforeyour GP when you anticipate anaddition to your family.

StanceIndustry having patient data is a riskworth taking – given the immensepotential benefits. Industry wouldbenefit – and societies, globally.This outline is simplistic; industrialleaders must be mindful ofRealpolitik but, maybe, thepharmaceutical industry,indisputable health benefactor,should be more bullish.

Malcolm E. Brown

bottled brown

EIPG Pharma Weekly RoundupClaude Farrugia, Vice-PresidentCommunications, has organised a newaddition to our publication line-up. The“Pharma Weekly Roundup” is anelectronic Sunday weekly issued byEIPG presenting a summary of newitems related to the pharmaceuticalindustry from the preceding week. Youcan access the latest and precedingissues and subscribe to emailnotifications of future issues, athttp://paper.li/EIPGeu/1403883135. Weshould be pleased to receive yourcomments on this publication.

PHAR-IN Competencies inBiotechnology – we need yourresponseThe PHAR-IN Consortium is aiming toproduce cutting edge continuingeducation courses for staff working inthe biotechnology industry. Followingour pilot, we need to obtain 500+responses from individuals working inthe pharmaceutical industry.

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Individual responses can be from anumber of staff members of the samecompany, in any area, from research anddevelopment to production and qualityassurance as well as sales andmarketing, company agencies, medicalinformation, training and regulatoryaffairs. To be statistically appropriate, weneed a number of individual responsesfrom each of our Member Associationcountries. Replies should be sent in by30 September.Based on your responses, we expect

to produce courses for continuingprofessional development, a taughtdistance learning Masters and units ofcourse study for undergraduates. Pleasecomplete the questionnaire irrespectiveof whether you currently work in thebiotech industry.

Online training for industrialpharmacy practice fromPharmaConsultPharmaConsult has announced their firstseries of short courses and webinarsspecifically prepared to help in theimplementation of new regulations andguidelines. As regulatory issues arise,fresh e-Learning courses andaccompanying webinars will beintroduced. Initially, the courses will be in

the English language but Spanishtranslation is planned for the near future.Any member of their National

Association interested in taking one ofthe PharmaConsult courses canpurchase at a discounted rate, if they goto the Members Area of the EIPGwebsite at http://eipg.eu/ and scrolldown to the Members Area and add thepassword which is available from yournational representative or from JaneNicholson ([email protected])In the Members Area, the

PharmaConsult on-line trainingcatalogue of e-Learning courses can befound. These include an Introduction toGMP, GMP for Biotechnology Products,Quality Management Systems, Basics of

ICH-GCP, an Introduction to MedicalDevices in the UK and the USA. A shortvideo about each course is availableand can be run before decidingwhether to buy.

Technical Workshop on CPDand LLL for HealthProfessionals Anni Svala, Vice-President Educationand Training attended a workshop oncontinuous professional development(CPD) and lifelong-learning (LLL) forhealthcare professionals. Her report isshown below.

Jane Nicholson, Executive DirectorEIPG, [email protected]

news from the EIPG

Report on a Technical Workshop from Anni SvalaA technical workshop on continuous professional development (CPD) and lifelong-learning (LLL) for healthcare professionals in Europe was organised on the 20 June inBrussels. Over 70 healthcare professionals gathered together to discuss thedifferences and needs of CPD among European countries. EIPG was invited torepresent the views and ideas of industrial pharmacists and Mrs. Anni Svalaparticipated in the event on behalf of EIPG. Significant differences in CPD in healthcare exist in European Union (EU), EuropeanFree Trade Association (EFTA) and European Economic Area (EEA) countries and thereis a lack of comprehensive studies that allow comparison and meaningful dialogueacross countries and professions1. In this context, the consortium consisting of theCouncil of European Dentists (CED), the European Federation of Nurses Associations(EFN), the European Midwives Association (EMA), the European Public Health Alliance(EPHA), and the Pharmaceutical Group of the European Union (PGEU), led by theStanding Committee of European Doctors (CPME) were contracted by the Consumers,Health and Food Executive Agency (CHAFEA) and funded by the Health Programmeto carry out a 12-month study concerning the review and mapping of CPD and LLL forfive health professions (doctors, nurses, dentists, midwives and pharmacists) in EU,EFTA and EEA countries.The technical workshop brought together experts and stakeholders in the area of CPDfor the five sectors of health professions, including representatives of professional andregulatory bodies, CPD providers, academics, accreditation bodies, relevant EUprojects and initiatives, and the European Commission1. The participants commentedand evaluated the initial findings of the study and provided information to fill any gapsin the data collected. The structure of the workshop allowed for active involvement of the participants,particularly through four parallel breakout sessions which were designed aroundhorizontal issues. The total number of participants of the individual breakout sessionswas limited to stimulate dialogue and discussion. Results of the workshop will beprocessed, together with the findings of the literature reviews and the survey, into afinal report for the study in October 2014, which will include policy recommendations.Finally, some personal comments on the workshop. The event was well-organised andthe agenda for the day was very comprehensive and nicely structured. It wasinteresting to see how continuous professional education and self-development is apart of professional identity among all healthcare professionals in Europe and theissues and concerns we are struggling with can be shared. By gathering together, weare able to discuss and raise the important questions to be solved. By sharingthoughts and ideas, we can learn from each other and are able to further improve ourtools for CPD and LLL. Most importantly, we will come closer and collaborate!

Reference:1 European Commission. EAHC/2013/Health/07 Study concerning the review andmapping of continuous professional development and lifelong learning for healthprofessionals in the EU: D.2 Discussion Paper, 3 June 2014. Luxembourg: ExecutiveAgency for Health and Consumers, EC.

european INDUSTRIAL PHARMACY September 2014 • Issue 22 19

eventsSEPTEMBER22-24 September 2014 – Vienna,AustriaQuality by Design - NewConcepts for Chemical andBiotech Product Developmentand Optimisationwww.diahome.org

25–26 September 2014 –Valencia, Spain3rd International Summit onGMP, GCP & Quality Controlwww.pharmaceuticalconferences.com

29 September 2014 – London, UK5th Annual Biosimilars &Biobetterswww.smi-online.co.uk

29 September–3 October 2014 –Boston, MA, USA12th Annual Cold Chain GDP &Temperature ManagementLogistics Global Forumwww.coldchainpharma.com

OCTOBER1–2 October 2014 – Heidelberg,GermanyGMP for Medical Deviceswww.gmp-compliance.org

1–2 October 2014 – Barcelona,SpainQuality by Design inPharmaceutical Analysiswww.gmp-compliance.org

6–8 October 2014 – HuntingtonBeach, CA, USA2014 PDA Universe of PrefilledSyringes and Injection Devices –Improving Patient Outcomesthrough Innovation www.pda.org

7–8 October 2014 – Dessau-Ro�lau (nr Leipzig), GermanyVaccines and Biologics – 10thBioProduction Forumwww.gmp-compliance.org

7–9 October 2014 – Paris, FranceCPhI Worldwidewww.cphi.com

8–9 October 2014 – London, UKPharma Compliance 2014www.healthnetworkcommunications.com

8–9 October 2014 – Barcelona,Spain11th Annual BioProduction2014www.informa-ls.com

8–9 October 2014 – Barcelona,SpainFlexible Facilities &Manufacturing of the Futurewww.informa-ls.com

12–15 October 2014 – Las Vegas,USA2014 ISPE Annual Meetingwww.ispe.orge

14–15 October 2014 – Berlin,GermanyPharmaceutical Cold & SupplyChain Logisticswww.pda.org

NOVEMBER2–5 November 2014 – Chicago,MI, USAPharma EXPOwww.ispe.org

4–5 November 2014 – Munich,GermanyParenteralswww.pda.org

4-6 November 2014 - Geneva,Switzerland5th Annual PharmaceuticalSerialisation and TraceabilitySummitwww.pharmaserialisation.com

5–7 November 2014 – Vienna,Austria17th APIC/CEFIC EuropeanConference on ActivePharmaceutical Ingredientswww.gmp-compliance.org

11–12 November 2014 – Geneva,SwitzerlandWorld Biosimilar Congress 2014 www.terrapinn.com

12–14 November 2014 –Brussels, BelgiumWorld Orphan Drug Congress www.terrapinn.com

12–13 November 2014 – Prague,Czech Republic Setting Specifications andAcceptance Criteriawww.gmp-compliance.org

13–14 November 2014 – Prague,Czech RepublicStability Testing for DrugSubstances and Drug Productswww.gmp-compliance.org

19 November 2014 – Düsseldorf,GermanyPharmaLab Congresswww.pharmalab-congress.de/ple_home.html

19–20 November 2014 – Berlin,GermanyAnnex 15 Conferencewww.gmp-compliance.org

27–28 November 2014 – Vienna,Austria9th Qualified Person Forumwww.qp-forum.org

DECEMBER2–3 December 2014 – Berlin,GermanyOutsourcing/ContractManufacturingwww.pda.org

9-12 December 2014 – London, UKGood Manufacturing Practice(GMP) and Good DistributionPractice (GDP) Symposium 2014www.mhra.gov.uk

10–11 December 2014 –Heidelberg, Germany Rapid Microbiological MethodsConferencewww.rmm-conference.org

11 December 2014 – London, UKStability Challenges Part II:Assuring the Stability ofMedicines from Manufacture toClinical Usewww.jpag.org


european industrial pharmacy issue 22 (september 2014)

Documents

ian moss6 life sciences

issue butcreate

years events

marianne anderssonswitzerland

ales francdenmark

shilpa gohil

janet hallidaygreece

ioannis nikolakakishungary