PrimarypackaginganddrugdeliverydevicesTrends in the pharmaceutical market and implications for the supplier industry

Andreas Neumann . Gerresheimer AG, DuesseldorfKorrespondenz:AndreasNeumann, Gerresheimer AG, Benrather Str. 18-20, 40213 Düsseldorf;e-mail:A.Neumann@gerresheimer.com

IntroductionAccording to the World Health Or-ganization (WHO) the worldwide ex-penditures on health in general grewfrom US$ 4.4 trillion in 20051) to US$6.5 trillion in 20122), which translatesto a compound annual growth rate(CAGR) of 6 %. Respectively, thespending on medicines showed acomparable increase during this pe-riod of time. Following data of theIMS Institute for Healthcare Infor-matics the pharmaceutical marketgrew even slightly faster at 7 % –8 % (CAGR from 2005 to 2011).3) Un-doubtedly, historical data are alwaysimportant and trends can be derivedfrom them. However it is also truewhat Wayne Gretzky, Canadian icehockey icon, said: “I skate to wherethe puck is going to be, not where ithas been.” Thus, consulting latestforecast figures for the global phar-maceutical industry allows for an es-timate of 4 – 6 % CAGR – resulting inan overall worldwide spending vol-ume on medicine of US$ 1.2 trillionby 20164), or respectively US$ 1.6 tril-lion by 2020.5) Other sources indicateworldwide prescription drug saleswill grow at around 4 % CAGR be-tween 2012 and 2018.6) Global mega-

trends such as population growthand demographic change will resultin rising demand for medication andwill furthermore make this devel-opment relatively immune to eco-nomic cycles, like they did in thepast.7) Within these general trendsthe pharmaceutical market is gainingevermore complexity. Herein we canidentify factors, which allow us toderive several implications for indus-tries upstream the pharmaceuticalsupply chain. Some of the key devel-opments and their direct or indirectimpact on the areas of primary pack-aging and drug delivery devices willbe examined in more detail in thisarticle.

Pharmerging MarketsThe pharmaceutical market is goingthrough a transformation on a largescale, with quite a decent shift of re-gional focus. There is a substantialtransfer towards the emerging mar-kets observable, as the developedwestern countries slow down. Thisgrowth is mainly driven by the con-tinued positive development in thePharmerging markets.8) While

growth in developed markets9) is rel-atively flat10) – a solid double digitgrowth of 13 % – 14 % from 2011 to2016 can be identified in these com-parably young markets. Primarily theBRIC countries (Brazil, Russia, India,China) are driving this devel-opment11). In 2016 the mature sectorwill then account for ‘only’ 57 % oftotal spending (down from 73 % in2006), while Pharmerging marketswill reach 30 % of global expenditure(cf. Figure 1).12) According to recentlypublished figures from IMS, Phar-merging countries will all togetheradd US$ 187 billion in annual salesbetween 2012 and 2017. This is twothirds of global pharma growth andwill increase the Pharmerging mar-kets’ global share from 23 % in 2012to 33 % in 2017, with all 4 BRIC coun-tries in the top 10 by sales value(China will account for the bulk ofthis growth) (Figure 2).13) In theseemerging countries populationgrowth is most evident14) and accom-panied by a prospering level ofwealth – expressed by a growingmiddle class in this sector (cf. Fig-

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1) World Health Organization 2005.2) World Health Organization 2012a.3) IMS Institute for Healthcare Informatics2011; IMS Institute for Healthcare Informatics2012.4) IMS Institute for Healthcare Informatics2012.5) PricewaterhouseCoopers 2012.6) Evaluate Pharma 2013.

7) Davis/ Philips 2007 and N.N. 2013a.8) Term coined by IMS: Pharmerging countriesare defined as those with >$1Bn absolutespending growth over 2012-16 and which haveGDP per capita of less than $25,000 at pur-chasing power parity (PPP). Tier 1: China; Tier2: Brazil, India, Russia; Tier 3: Mexico, Turkey,Poland, Venezuela, Argentina, Indonesia,South Africa, Thailand, Romania, Egypt, Uk-raine, Pakistan and Vietnam, IMS Institute forHealthcare Informatics 2012.

9) Developed markets are defined as the U.S.,Japan, Top 5 Europe countries (Germany,France, Italy, Spain, UK), Canada and SouthKorea, IMS Institute for Healthcare Infor-matics 2012.10) PricewaterhouseCoopers 2012.11) IMS Institute for Healthcare Informatics2012.12) IMS Institute for Healthcare Informatics 2012.13) IMS Health 2013.14) United Nations 2013.

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ure 3).15) With that millions morepeople are gaining access to basicmedicines. As a result, generalgrowth in medication volumes perse and hence increasing demand forprimary packaging and drug deliverydevice units is foreseeable.16) In orderto serve the industry’s needs, sup-pliers need to be present where phar-maceutical manufacturers are.Therefore, global presence and localproximity are essential for a reliablesource of supply, ensuring smoothoperations at the filling line. More-over a robust risk assessment andrisk-management capabilities acrossthe extended supply chain have be-come an essential part of a pharma-ceutical company’s sourcingstrategy.17) Consequently the exist-ence of several production plantsmeans risk mitigation through backup capacities of upstream products.

Developed MarketsAs mentioned above – growth ratesin mature markets are comparablyflat. However, this does by no meansimply that these still very importantmarkets18) are stagnating. They arerather developing differently and un-dergo significant alterations them-selves. “It`s not how old you are, it`s

how you are old” (Jules Renard,French Author). First and foremostdeveloped countries suffer mostfrom the often cited demographicchange and the resulting aging pop-ulation (cf. Figure 4).19)

Additionally epidemiological fac-tors play a key role. Thus “rich peoplediseases” like obesity and diabetesare major problems for the devel-oped countries. This outlook trans-lates to an increase of chronic dis-eases diagnosed.20) Obesity and ageare both closely linked to more dis-eases and, sure enough, epidemicslike diabetes, cardiovascular diseasesor hypertension are permeating thewestern hemisphere.21) According tothe worldwide Diabetes Atlas of theInternational Diabetes Federationone adult in ten will have diabetesby 2030.22) In the US around 11 % ofthe adult population are reporteddiabetics – rising to some 27 % ofthose aged 65 and older.23) Accord-ingly healthcare cost are rising24) andare condemned to do so further up toan unsustainable level. Following cal-culations of CEPTON Strategies, costwould reach 30 % of total GDP – ifhealthcare expenditure continuedsimply following demographics.25)

This trend reflects growing cost pres-sure and further need for outpatientand home care that does not require

an overnight stay in a hospital. Moretherapies are being carried out in apatient’s private surroundings. Agrowing number of drug regimensadministered at home then againimply new challenges. For one, theneed of protecting the youngest gen-eration from accidentally taking themedicine requires more child resist-ant packaging solutions (cf. Figure 5).

In light of the above describedaging population the older genera-tion needs to be provided with seniorfriendly packaging features, to enablethe elder to conveniently access andadminister their therapeutics (cf. Fig-ure 6). A combination of child pro-tective and senior friendly packagingis a major challenge to address forthe market players.

By all means, within the non-clini-cal settings at the patient’s home, theprocess of self-administration26) ofdrugs is inherent.27) To support an ac-curate therapy via self-medication thedrug delivery device and its design aretherefore –more than ever – playing amajor role. Human factors and a pa-tient centric design approach are keyto enhance convenience and ensurethe necessary precision of dosage. Tosecure and leverage proven expertisein the field of packaging and deliverydevice design and industrial scale up(while at the same time being betterable to focus on the core business),partnering is clearly a solution forpharmaceutical companies.28) Longerterm relationships and co-devel-

TechnoPharm 4, Nr. 3, 138–148 (2014)© ECV . Edit io Cantor Verlag, Aulendorf (Germany) 139Neumann . Primary packaging and drug delivery devices

Figure 1: Spending on medicine by geography.

Figure 2: Pharmerging markets sales & growth.

Figure 3: Global middle class.

15) The size of the “global middle class” willincrease from 1.8 billion in 2009 to 3.2 billionby 2020 and 4.9 billion by 2030. The bulk of thisgrowth will come from Asia: by 2030 Asia willrepresent 66 % of the global middle-classpopulation, Pezzini 2012.16) Freedonia 2013.17) PricewaterhouseCoopers 2011.18) Canada, France, Germany, Japan, the UKand US still represent 59 % of the industry’stotal revenues, cf. PricewaterhouseCoopers2012.

19) United Nations 2013.20) Wenninger et al. 2011.21) Bangert 2013.22) International Diabetes Federation 2012.23) PricewaterhouseCoopers 2012.24) Greystone Associates 2013.25) Müller 2012.

26) This means patients have to administertheir medications themselves – without thehelp or supervision of a healthcare profes-sional.27) Kelly 2013; Research and Markets 2013.28) N.N. 2012a.

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opment with partners that are savvy indesign, development, tooling and highquality serial production can be iden-tified as one main future stream in theindustry. According to a recent studypublished by Transparency MarketResearch, the global medical devicesoutsourcing market is expected togrow at a CAGR of approx. 12 % fromUS$ 21.1 billion in 2012 to US$ 40.8billion in 2018. Within this devel-opment, the product design segmentholds the largestshare with 29 %.29)

Evaluate Med-Tech predicts~4 % CAGR forthe drug deliverysector from 2011– 2018.30) Theneed for a morepatient-centricapproach in thedesign of primarypackaging andespecially of drugdelivery devices isalso reflected by the general trend to-wards personalized medicine. Movingaway from ‘one size fits all’ this modelof customized healthcare is aiming atmeeting more patient-group specificneeds (cf. Figure 7).31)

By the sametoken this devel-opment pro-motes a trend inthe direction ofmore individuali-zation in devices.Not least becausethe delivery de-vice is more oftena patient’s com-panion for manyyears and hencealso a lifestyleproduct thatneeds to be de-signed accord-ingly.

The above stated fact that med-ications are more and more oftentaken at home and without the su-pervision of a healthcare professionalpresents another challenge – a pa-tients’ adherence to pharmaceuticalcare.32) Already today the rate of ther-apy compliance is low. Patients – fora variety of reasons33) – not stickingto their medication plan, cause tre-mendous costs to a society’s health-care system. A 2013 study of the IMS

Institute for Healthcare Economicsidentifies an US$ 475 billion annualcost saving opportunity from usingmedicines more responsibly. Follow-ing this report non-adherence to

medication provides the biggest leverto tackle the situation (cf. Fig-ure 8).34) Enhancing adherence in-volves complementary use of ed-ucative, practical and emotionallyas well as behaviorally supportive in-terventions. An increased level of in-formation to improve transparencyand to integrate the patient can beunderstood as one practical ap-proach of advancing compliance. Ahigher level of information pairedwith a memory function can beachieved for instance by a dosecounter functionality on an inhaleror other mechanical or electronicfunctions. In these regards the mar-ket will likely develop a demand of asmarter generation of primary pack-

aging and drug deliv-ery devices.

To give an exam-ple for an emotionalinhibition threshold,preventing a patientfrom taking its med-ication one can citeneedle phobia. “Vic-tims of needle phobiapossess a high risk ofmorbidity and mor-tality as they avoidhealth care. The etiol-ogy of needle phobia

lies in an inherited vasovagal reflexof shock, triggered by needle puncture.Individuals who inherit this reflexlearn to fear needles through succes-sive exposures to needles.” 35) To cir-cumvent the puncture by a cannulathere are alternative technologies for

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TechnoPharm 4, Nr. 3, 138–148 (2014)© ECV . Edit io Cantor Verlag, Aulendorf (Germany)140 Neumann . Primary packaging and drug delivery devices

Figure 5: Child resistant packaging – closures(Quelle: Gerresheimer AG).

Figure 6: Senior friendly packaging (Quelle: Gerresheimer AG).

Figure 4: Median ages of the world.

29) Transparency Market Research 2012.30) Evaluate MedTech 2012.31) Müller 2012.

32) Referring to a patient who does not take aprescribed medication or follow a prescribedcourse of treatment, cf. Nichols-English/ Poi-rier 2000.33) Buston/ Wood 2000; Taddio et al. 2012;Nichols-English/ Poirier 2000.

34) IMS Institute for Healthcare Informatics2013.35) Hamilton 1995.

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drug delivery available on the market(cf. Figure 9). A report by Visiongainpredicts the global needle-free deliv-ery devices market to be worth al-most US$ 5.9 billion by 2022. Themarket generated sales of US$ 950million in 2010 (16 % CAGR).36) How-ever, needle free does not necessarilymean painless37), and in additionwith delivery requirements of certainmolecules and larger volume injec-tions38), this segment is facing itsown challenges. Therefore, anotheralternative for needle phobic pa-tients might lie in the advent ofmicro-needles to deliver compoundsinto the highly vascularized dermis.By entering the yet relatively under-developed market (according to

Dubin, a re-port fromGreystone As-sociates wouldput the micro-needle drugdelivery mar-

ket at just under US$ 400 millionglobally by 201239)), pharmaceuticalcompanies can differentiate their of-fering with a patient-friendly, easy-to-apply, low-hazard system.

In an assessment of the developedmarkets we – at this point – also needto emphasize the general trend to-wards higher quality standards andincreased pressure from the legislativeauthorities.40) The pharmaceutical in-dustry is experiencing a period ofheightened regulatory scrutiny – orig-inating in the developed countries andeffective globally.41) As a consequencespecifications and requirements forthe packaging and administration de-vices of pharmaceuticals become

tighter and grow in importance –working with an experienced partnerenabling compliant packaging anddrug delivery solutions is of para-mount importance.

Last ing Patent Cliff &Genericizat ionOne of the most relevant trends forthe pharmaceutical industry in gen-eral and for ‘Big Pharma’ in particu-lar, is the Patent Cliff 42). While thefirst slump hit with some estimatedUS$ 30 billion branded sales loss in2012 – which was as steep as neverseen before in the industry – theyears to come threaten with equallyscary sales at risk (cf. Figure 10).43) 44)

The expiration of a patent on ablockbuster drug can easily impacta pharmaceutical company’s bottomline negatively into the billions45)’ 46).

“If you’re going through hell – keepgoing”

– Winston Churchill, English states-man

Being well aware of this trend, theindustry is as anxious as ambitious tonavigate the patent cliff and investaccordingly. Figure 1147) illustratesthe market launches of Europeanpharmaceutical companies in the

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Figure 7: Scope of Personalized Medicine.

Figure 9: Needle-free injection system(DosePro® Zogenix) (Quelle: Gerresheimer AG).

Figure 8: Avoidable healthcare cost – non-adherence is the biggest lever.

36) Visiongain 2012.37) Chavan et al. 2013.38) Tagawa et al. 2012.

39) Dubin N.D.40) Moore 2013.41) PricewaterhouseCoopers 2013.

42) a colloquialism to denote the potentialsharp decline in revenues upon patent expiryof one or more leading products of a firm, cf. N.N. 2013a.43) Iskowitz 2013.44) Evaluate Pharma 2012.45) Carroll/ Palmer 2012.46) Stone 2013.47) Henderson, BoA Merrill Lynch 2013.

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years past and gives a prognosis oflaunches in the near future. In the U.S the Food and Drug Administration(FDA) approved 39 new molecularentities (NMEs) in 2012 – the mostin 16 years. This trend would suggestthat pharmaceutical players arepoised for growth after losing billionsof dollars in recent years to genericcompetition.48) Most drug makers arealso better prepared now and it isanything but rare to see them break-ing the old ‘Blockbuster-mentality’by introducing new business modelsand thus decreasing their depend-ency on only few products49). Thisshift towards more diverse port-folios50) also requires a wider rangeof diversity regarding packaging.

Despite the fact that ‘Big Pharma’is obviously better prepared (the Pat-entCliff did not come unannounced)it is generally true to say that Ge-neric’s growth with solid double digitrates in recent years was more thantwice as strong than for the totalpharmaceutical industry, hence ageneral movement towards Genericsis evident in the market (cf. Fig-ure 12).51)

This trend is inevitably leading toincreased volumes of Generic units

sold. In 2011 already close to 50 %of the pharmaceutical market’s vol-ume (as opposed to its value) con-sisted of Generics – and the trendline is rising (cf. Figure 13).52)

As a consequence one can read offthis trend, there is stronger growth inprimary packag-ing volumesforeseeable. Inthe course ofthis “Genericiza-tion” packagingplays an increas-ingly importantrole. Since ge-neric productsare – as a gen-eral rule – aim-ing at providingmore cost-effec-tive alternativesto originatorbrands, thepackaging solu-tions for thesedrugs are ratherstandardized, high volume commod-ity. By the same token however theyare providing qualitative protectionand delivery of drugs to patients.The surge of copycat drugs alsodrives interchangeability of products.It is therefore of growing importanceto demarcate otherwise similar prod-

ucts from one another. Mee-tooproducts in the biotech area for ex-ample may use different drug deliv-ery devices than their reference bio-logic originator product.53) Drug de-livery devices will be a key part of thebiosimilar package required to differ-entiate from the competition54) in amarket promising significant volumeeffects (as observed with G-CSF inthe UK and Sweden55)). Accordingto data from IMS this could driveup biosimilars’ market growth con-siderably (cf. Figure 14).56)

OriginatorDrugs, NewLaunches&SpecialtyTherapiesBy investigatingthe geographicalorigin of newchemical en-tities (NCEs)launched, wecan see belowin Figure 1557)

that developedcountries – byfar – still playthe leading role.As a matter offact, this is

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TechnoPharm 4, Nr. 3, 138–148 (2014)© ECV . Edit io Cantor Verlag, Aulendorf (Germany)142 Neumann . Primary packaging and drug delivery devices

Figure 10: Patent cliff.

Figure 12: Generic sales and growth vs. totalmarket growth.

Figure 11: Filled pipelines.

48) Palmer 2013.49) Bangert 2013.50) PricewaterhouseCoopers 2011.51) Lewis 2013. 52) IMS Health 2011b.

53) Taylor 2012.54) Rotenstein et al. 2012.55) IMS Health 2011a.56) IMS Health 2011a; SU = Standard Unit =The number of standard “dose” units sold; G-CSF = Granulocyte colony-stimulating factor =a glycoprotein that stimulates the bone mar-row to produce granulocytes and stem cellsand release them into the bloodstream.57) IMS Health 2013.

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mostly due to significantchallenges regarding af-fordability, protection ofintellectual property anddelays new drugs face inPharmerging markets.

This trend is also re-flected by the productmixes in Pharmerging anddeveloped markets, whichhave developed very differ-ent from one another. Mostof the top 20 brands inPharmerging are olderproducts (a large numberof them > 20 years, someeven 30+ years), targetingchronic diseases (like hy-pertension and diabetes).In the top 8 mature mar-kets there is not a singledrug among the top 20 thathas been launched morethan 20 years ago.58) Ven-turing an outlook on theglobal development we will– by tendency – see thehighest increase in the areaof specialty drugs59) (cf.Figure 16).60)

The sustainable growthin the biopharmaceuticalsector yields potent drugswith a highly selective action. How-ever these protein and peptide baseddrugs are complex molecules. Devel-oping, storing and eventually deliver-ing such therapeutics is challenging inmany ways – especially regarding sta-bility, pharmacokinetics and bioavail-ability.61) Due to their specific prop-erties biotech drugs require sophisti-cated drug delivery and primary pack-aging systems.

Drug delivery devicesSince the route of delivery of spe-cialty therapies is almost exclusively

via parenteral injection62), drug deliv-ery devices are being taken more intoconsideration and already at an earlystage in the development of innova-tive medication. Following the abovestated trend of individualization inhealthcare, there will prospectivelybe smaller patient target-groups.This meansmore specific devices willevolve, leading to a greater diversityin form and design (cf. Figure 17). Wewill see further ergonomic shapesand functions, addressing humanfactors and permitting individual, ac-curate dosage for patients that mayhave an impaired motor functionand self-administer their drugs in anon-clinical setting. Furthermorethis innovative market environment– along with the industry leaving the

blockbuster path and fo-cusing on tighter disorderpatterns like orphan dis-eases – will result inshorter product lifecycles.

Moreover, branded orig-inator products face a ris-ing need of differentiationand lifecycle managementbecause of the generic andbiosimilar competition (asoutlined above).63) As an in-stance of managing a prod-uct’s lifecycle the switch ofan injectable therapy’s pri-mary packaging containertowards more sophisti-cated system (e. g. from avial to a prefilled syringe),is still instrumental to opti-mize lifecycles. Althoughthe drug is normally stillunderstood as the mainproduct differentiator, thedrug delivery device is be-coming increasingly impor-tant as another means ofdifferentiation in morecompetitive markets.64)

Protecting a treatment ascombination product65)

(by competition law) canprovide a major competi-

tive edge to the pharmaceutical com-pany and also enhance a drug’s eco-nomic lifecycle.

Primary packagingAlready for decades Type I Borosili-cate Glass66) provides several benefitsto manufacturers of parenterals. It isof transparent clarity and thereforeallows for visual inspection of thedrug; it is inert against most sub-

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Figure 13: Share of generics: value vs. volume.

Figure 14: Volume effect after the introduction of biosimilars.

58) IMS Health 2013.59) Specialty therapies are products which areoften injectables, high-cost, biologic or re-quiring cold-chain distribution, cf. IMS Insti-tute for Healthcare Informatics 2012.60) IMS Institute for Healthcare Informatics2012.61) Sacha et al. 2010.

62) IMS Institute for Healthcare Informatics2012.

63) Dubey/ Dubey 2009.64) Simpson 2012.65) Combination products are therapeutic anddiagnostic products that combine drugs, de-vices, and/or biological products. FDA expectsto receive large numbers of combinationproducts for review, cf. FDA 2013c.66) Borosilicate glass is characterized by high-est hydrologic resistance and lowest alkalileakage. It is regulated by three internationalpaharmaceopoeias (USP, EP and JP) as well asthe international standards ISO 719/720 andISO 4802-1, cf. Petersen 2012.

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stances and stable almost infinitely,which translates to best conditionsfor storing and a long shelf-life. Itsimpermeability to water vapor andgases is adding to the expediencyfor injectable solutions. Togetherwith the comparably long history ofActive Pharmaceutical Ingredient(API) on the market with this mate-rial, the relatively favorable priceproves that it is an excellent and last-ing packaging solution.67) However,there are also shortcomings whichbecome even more important withregards to highly potent and sensi-tive modern drugs. Glass is compa-rably fragile and can break on theimpact of mechanical stress.68) Alsothe surface properties of a glass con-tainer are of utmost importance, par-ticularly on the inner side in contactwith the product. Extractable metalions may leach depending on the pHvalue. Aqueous parenteral solutionswith a pH value > 7 attack the glasssurface. Under such circumstancesthe glass structure releases metalions with potential adverse effectson the stability of sensitive biotechdrugs.69) In this context there is aneed to debate the topic of delami-nation, where glass flakes may elutefrom the glass matrix’ surface andthus contaminate the drug.70)

Specialtydrugs like bio-logics are mostlyvery expensive.One vial caneasily cost sev-eral hundredsor even thou-sands of dollarson the market.71)

Hence breakingglass duringprocessing (filli-ing – especiallyalso in light ofprocess containment for productionof cytotoxics), or adulteration of thecompound (through extractablesand leachables) or contaminated so-lutions (by delamination) couldcome dearly expensive to the indus-try.72) Advancements in therapeuticsand diagnostics yielding highly po-tent drugs should be responded toby innovations in the area of primary

packaging and delivery systems.Therefore innovative materials likecyclo olefin polymers/ copolymers(COP/ COC)73) are explored andpromise to be a valid packaging al-ternative. Differently to glass, COP’sbreak resistance is higher, the rangeof pH-value tolerance is wider andthere is no peril of potentially leakingmetal ions. The appeal of the poly-mer packaging solution lies also in itsexcellent drainability properties,which is particularly important forexpensive biotech drugs.74) At the

present timeCOP is primarilyused for themanufacture ofvials and sy-ringes. Lookingat the latter wecan state furtherbenefits of thepolymer overglass. Whereasfor productionand later appli-cation of prefil-lable glass sy-

ringes the use of glue, tungsten andsilicon is necessary, there is no needfor tungsten and glue in the fabrica-tion of COP syringes. Additionallyless siliconization (which is used toensure full functionality of glass sy-ringes, but could also cause aggrega-tion of proteins) is needed.75)

However advantageous polymersmay be, there are also considerable

downsides to COP containments. Onthe one hand they are more scratch-prone than glass, and on the otherhand they are significantly more per-meable to gas and water vapor. Overa products shelf life oxygen permea-bility may infringe sensitive proteinsand water vapor may have undesiredeffects on hydrophilic substances likelyophilized compounds.76) To over-come these deficits containers witha multi layer structure have been de-veloped to address the current mar-ket needs. Figure 18 shows the com-bination of a COP and a polyamide(PA) layer. The advantages of this de-sign are the enhanced break resist-

TechnoPharm 4, Nr. 3, 138–148 (2014)© ECV . Edit io Cantor Verlag, Aulendorf (Germany) 145Neumann . Primary packaging and drug delivery devices

Figure 17: Diversity of medical Devices – providing differentiation opportunities(Quelle: Gerresheimer AG).

Figure 15: Global launch sales.

Figure 16: Spending and growth in leadingtherapy areas.

67) Petersen 2012.68) Sacha et al. 2010.69) Dirk 2011.70) Petersen 2012.

71) N.N. 2012b.72) Dirk 2011.73) Cyclo olefin polymers are thermoplastichydrocarbon polymers with a cycloaliphaticstructure in the main chain, cf. Petersen 2012.74) Dirk 2011.

75) Jones et al. 2005.76) Petersen 2012.

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ance (Multilayer vials demonstrateup to 10 times higher impact resist-ance compared to glass vials), thesignificantly better barrier propertiesthan ‘single layer’ plastic vials (en-sured by the PA layer), and at thesame time glass-like transparencywithout metal ion release.77) Two fur-ther major arguments pleading forpolymer usage for high value drugsare its low adsorption of protein-likemolecules and its excellent drainabil-ity. It has been scrutinized that –depending on the surface of thematerial in contact with the drug –adsorption of molecules can happen.Representative studies show an ex-emplary loss of nine per cent of amodel molecule due to adsorptiononto a glass surface.78) Less moleculeloss and a higher drainability requireconsiderably less overfill (which isnormally performed to ensure ther-apy efficiency). This in turn trans-lates to significant cost reductionfor the biopharmaceutical companywhich should easily compensate thehigher price of multilayer plasticvials.The area of high price specialty drugsis increasingly becoming subject tocriminal business practices. Counter-feit medicines79) of high value origi-nator products provide a profitable

opportunity toforgers and arebeing detectedmore and morefrequently.

“Fake is as oldas the Eden tree.”– Orson Welles

In the cause of2012 the FDA is-sued a series of al-erting letters con-cerning bogus on-

cology drugs.80) Authorities like In-terpol or the WHO state that theprevalence of fake drugs is growingin general.81) In this context anti-counterfeiting packaging is playingan increasingly important role to en-sure drug integrity. Hence there areseveral features for different packag-ing types readily available for the in-dustry. On item level we can observethe widening use of stand-alonetamper-evident closures for drugcontainers themselves (cf. Figure 19).

Additionally there are solutions

rising in the marketplace that aresystemic and involve the whole phar-maceutical supply chain. These trackand trace approaches are not stand-alone, but need an accompanying da-tabase to verify a drug’s origin andauthenticity. The primary packagingcan be tagged with a data carriersuch as a 2D data matrix containingrelevant information and linking theproduct to the above mentioned da-tabase. The 2D code can either be

printed on or burned in with high-end laser coding technology (cf. Fig-ure 20). As an alternative mediumalso Radio Frequency Identification(RFID) tags represent powerful datacarrier solutions. According to re-cently passed legislation anyway,the topic track and trace is irrev-ocably gaining ground in the phar-maceutical industry.82)

In order to establish a successfulanti-counterfeiting strategy it is rec-ommendable to implement differentcountermeasures in combination. Asa basic rule we can say: The morelayers of security features that canbe implied, the more difficult theyare to copy and to overcome, hencethe more promising the anti-counterfeiting strategy.

Conclusion and Outlook“You must look within for value, butmust look beyond for perspective.” –Denis Waitley. The above outlinedtrends provide both, a challenging

surrounding aswell as promisingopportunities forthe pharmaceuti-cal packaging in-dustry in generaland for the mostinnovative and re-liable players inparticular. Thesubstantial shifttowards theemerging markets

together with global populationgrowth and improved access to med-ication will increase overall demandof packaging volumes. Local prox-imity of globally active suppliers isof key importance to participate inand benefit from these growth dy-namics.

At the same time it is paramountnot to neglect the developed mar-kets. However mature they seem,their patterns of reaching maturity– characterized by demographicchange, the rise of chronic diseases,

Drug Delivery Devices

TechnoPharm 4, Nr. 3, 138–148 (2014)© ECV . Edit io Cantor Verlag, Aulendorf (Germany)146 Neumann . Primary packaging and drug delivery devices

Figure 18: Mulitlayer parenteral vial (MultiShell®) (Quelle: Gerre-sheimer AG).

Figure 19: Tamper evident packaging solutions (Quelle: Gerresheimer AG).

77) Dirk 2011.78) Dirk 2011.79) Counterfeit medicine is fake medicine. Itmay be contaminated or contain the wrong orno active ingredient. They could have the rightactive ingredient but at the wrong dose.Counterfeit drugs are illegal and may beharmful to your health, cf. FDA 2013a.

80) FDA 2013b.81) Interpol 2013; World Health Organization2012b. 82) Helfand 2013; Vaczek 2013; Carrera 2013.

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prevailing pressure on healthcarecost leading to more home- andself-medication – provide major op-portunities for the manufacturer ofprimary packaging and drug deliverydevices. Human factors and a patientcentric design – coping with increas-ingly heterogeneous patients’ needs– are main principles of the future(not least also to improve patients’therapy adherence). As indicated wewill likely see more electronics in de-vices, culminating in further featuresallowing for online connectivity andin turns enabling physicians to mon-itor and treat their patients remotely.Moreover the ongoing increase inregulatory scrutiny will further de-mand highest quality at all stages ofthe pharmaceutical supply chain –especially also for packaging anddrug delivery solutions.

The prevailing patent cliff and thecorresponding change of businessmodels away from the ‘one-size-fits-all’ blockbuster strategy towardsmore specific therapies and patientgroups will presumably continue todrive a more diverse portfolio ofpackaging and drug delivery solu-tions. The closely related trend ofGenericization which will firstly andby nature increase the demand ofpackaging unit volumes will likewisecontribute to more differentiatedproducts.

The progres-sing advent ofspecialty bi-otech drugs –which gainground firstand foremost inthe developedmarkets – re-quire sophisti-cated primarypackaging anddrug deliverysystems. Ad-vancements inpharmacology and biotechnologycreating highly potent drugs needto be embraced by appropriate so-lutions of an equally innovative sup-plying industry. Within the rise ofspecialty therapies – that are mostlyinjectables – drug delivery deviceslike autoinjectors will be taken intoconsideration at an earlier stage ofthe drug development and will alsovery likely get a greater deal of at-tention while registered as combi-nation (drug-device) product. Fur-thermore the decision of the pri-mary packaging material is set tobecome more focused on. Abovestated advantages and disadvan-tages of several different subjectmatters justify the expectation of acoexistence of proven and reliableglass containers and innovative

mono- or multilayer polymer solu-tions.

Due to increasing environmentalpressures also sustainable processesand eco-friendly materials need to betaken into account. In light of theongoing distribution of fake med-icine and the closely related legis-lation in these regards, we saw thatdevelopments in anti-counterfeiting-and smarter packaging solutions willgain momentum. On item level onecan predict more features ensuringtemper evident or such character-istics providing for a drug’s trackand traceability.

In conclusion, the overall balanceof trends seems to allow for the state-ment that – although challenging –packaging is playing an essential partin the future of drugs.

Print-on Laser-codingFigure 20: 2D datamatrix application for track and trace(Quelle: Gerresheimer AG).

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