alternative for a cash-strapped and time-poor industry.

Despite these economics, a recentstudy of TMF-owners across the pharma,biotech and life sciences industries findsthat only 13% of drug developers haveadopted purpose-built electronic trialmaster files (eTMFs). The study, carriedout by Veeva Systems, sought tounderstand the barriers preventing drugdevelopers from taking advantageof eTMF applications that would stream-line many of the inefficient processes thatcan slow clinical trials. The resultshighlight some of the common challengescompanies face when undergoing majortransformations in their business-criticaltechnology, but also illuminate the long-term benefits pharma and biopharmacompanies stand to gain from makingstrategic investments in paperless TMF.

However, recognising the efficiencies

that an eTMF application offers anorganisation is one thing. Transformingan eTMF into a truly strategic assetcapable of improving the bottom line isanother matter. To extract the fullpotential of an eTMF, a life sciencesorganisation must take a few importantsteps with the partner, the applicationitself and its own organisation, theseinclude: Getting everyone on boardAccording to Veeva’s study, 69% ofrespondents say they rely on email toexchange trial documents with sponsorsor contract research organisation (CRO)partners. The biggest hurdles thatcompanies face when making thetransition to paperless TMFs is thecreation of a collaborative system that allstakeholders in the drug developmentprocess can access easily and securely.

Even when the sponsor and/or CRO ▼

With regulatory pressure mounting, pharma companies should need no help deciding to migrate topaperless trial master files. For those thinking about switching, Rik van Mol, Vice President of R&DStrategy, Veeva Systems, outlines the key considerations for making the transition

October 2014 manufacturing chemist 45

Time is money, and never has thecliché been more apt. With biotechpioneers spending an average of 10 yearsand more than US$1.2bn to bring a newtherapeutic to market, in recent yearsthere has been a particular focus onapplying technology (particularly Cloud-based tools) to the challenge of runningcosts and time-efficient trial processes.

So what are the issues that waste timeand leak value from the drugdevelopment process? In 2010, McKinsey& Company published a report thatfound mismanagement of the trial masterfile (TMF) was responsible for slowingdown trials by an average of 12 months,costing providers up to $2bn in lostrevenue for a blockbuster therapy.

Bearing these staggering figures inmind, it is little surprise that technologythat promises to bend both the time andcost curves down is an attractive

Cloud-basedeTMFs –less paper,more value

CLINICAL TRIALS

045-048 mc1014 veeva_Layout 1 18/09/2014 12:40 Page 45

CLINICAL TRIALS

46 manufacturing chemist October 2014

maintain an eTMF on their own network,access to outsiders is blocked. In thisscenario, stakeholders send documentsvia paper shipments or email andmaintain separate copies of TMFdocuments, which need to be reconciledat the conclusion of the trial. Alternately,a Cloud-based eTMF is, by its verynature, easily and securely accessible toall parties. Sponsors can define newprocesses that are more efficient upfront,maintain visibility throughout the trial,and help ensure that the TMF remainsinspection ready at all times. This type ofcollaborative and open process begins byuploading a document into a Cloud eTMFin real time.

Eldin Rammell, a clinical recordsmanagement expert and managingdirector at Rammell Consulting, says theresearch confirms that not all eTMFs arecreated equal. ‘Many eTMFs are simplefile shares that perpetuate manualprocesses,’ he said.

According to Veeva’s research, firmsusing mature technologies, specificallyprocess-driven eTMF applications andcontent management systems, reportgood or major improvement in misfileddocuments, compared with local filesystem users. Yet today only about one in10 respondents (13%) use eTMFapplications to manage their TMFs.Moving from ‘simple file share’ to arepeatable, Cloud-based eTMFframework improves quality anddecreases non-compliance.

Because all parties have direct access,physical distribution of content becomesobsolete, eliminating the need to emailcopies of documents as attachments.Managing collaborative processes withinthe eTMF combines informationexchange and tracking into a singlesystem. Not only does collecting TMFdocuments become more efficient, but allparties gain visibility into status andoutstanding tasks.

When developing a CRO-sponsorshared eTMF, both parties must establishtime frames for completing managementmilestones, as well as roles andresponsibilities for execution. In manycases, the responsibility for filing TMFdocuments and other content will shiftfrom a records management function tothe author/owner of the TMF.

Managing a successful process changeis critical for gaining many of the benefitsassociated with using an eTMF. Becauseof this, establishing a repeatableframework is an important part of thechange management process. Definingeach stakeholder’s role is also critical tosuccessful outsourcing, finds an AvocaGroup survey of 237 respondents.Collaborative relationships ‘require

absolute clarity in roles andresponsibilities and upfront planningassumptions,’ Avoca states. Typicalclinical collaborations have lacked thisclarity, sometimes resulting in difficultiesand disappointment in the relationship.Building a stable and replicablemodelBuilding a repeatable TMF frameworkinvolves defining expectations upfront toensure that all TMF participants arealigned and in agreement on what theTMF artifacts are called, when they aredue, and who is responsible for filingthem. In order to know what content ismissing or late, all contributors mustfirst understand what is expected. Arepeatable framework sets expectationsat the outset, reinforces the collaborativeprocess and improves overall efficiency.

Standardising a common nomenclaturedrives better communication byharmonising the filing efforts of diversestakeholders. When multiple parties referto items by different names, filing andtracking become confusing, increasingthe chance for error. The nomenclaturedefined by the Drug InformationAssociation’s (DIA’s) TMF ReferenceModel represents input from hundreds ofpharmaceutical companies, CROs,regulatory agencies and vendors fromacross the globe.

In addition to standardised naming,the TMF Reference Model introducesstandards for content, structure, andmetadata. For these reasons, more andmore clinical trial sponsors, including

Kythera, are leveraging this model tobuild their own repeatable frameworks.

Additional elements of the repeatableframework include configuring standardoperating procedures (SOPs) within theeTMF application, essentially codifyingthem into system workflows. The eTMFapplication orchestrates task completionacross companies and stakeholders, inkeeping with company SOPs. A commonworkflow automates many manual steps,improving productivity and trialefficiency. By comparison, a paper-basedTMF or eArchive relies on peopleremembering and following written SOPsand then documenting them.

When collaborative processes arecoupled with a repeatable framework, thefoundation is in place to begin definingand leveraging performance metrics.Avoiding non-compliance To meet the audit expectations of healthauthorities globally, moreorganisations are consideringadopting eTMF applications. The trendcan be likened to the industry’s movefrom paper case report forms (CRFs)to electronic data capture (EDC) a decadeago. The growth trend here is reflected inVeeva’s research, which finds thatcompanies with full eTMFs are twice aslikely to report audit-readiness as theirpeers relying on manual or paper-basedTMF systems.

eTMF reports such as study sitedocument status, site acknowledgementof investigators’ brochures and documentexpiration, can all help inspectionreadiness by providing greater visibilityinto what stages of the trial process arebeing inefficiently run, and what the trialowner can do to course correct.

These common, trial-specific metrics –efficiency and completeness – establish abaseline for improvement, allowingmanagers to look at metrics in anorganised way, as opposed toextrapolating from paper-based

“Managing collaborative processeswithin the eTMF combinesinformation exchange and trackinginto a single system. Not only doescollecting TMF documents becomemore efficient, but all parties alsogain visibility into status andoutstanding tasks”

Figure 1 Processes that would shorten clinical development times if paperless

▼

▼

045-048 mc1014 veeva_Layout 1 18/09/2014 12:40 Page 46

CLINICAL TRIALS

48 manufacturing chemist October 2014

processes. However, as more data iscollected over time and across multipletrials, it also becomes possible to identifytrends.

These benefits are being realised byeTMF operators in Veeva’s study. Thosecompanies that extensively use metrics toimprove the execution or design of trialprocesses are more than twice as likely toreport business improvements from theireTMFs as those not using metrics. Theseadvantages include better TMFdocument quality (63% and 29%respectively), audit readiness (56% and25% respectively), and increased SOPcompliance (49% and 16% respectively).

eTMFs allow TMF owners to defineSOPs for how any clinical document ismanaged, and therefore flag anymismanagement early. By creating rulesand definitions for SOPs, theeTMF creates ways to track applicationworkflows and identify noncompliantprocesses before the TMF is put beforeregulators for approval.

Veeva’s research finds that particularlyin the early stages of clinical trials, TMFowners with Cloud-based eTMFapplications are already improving theDIA and EMA’s submission processes.This is unsurprising when one considers

that e-submission protocol was developedin conjunction with the DIA and EMA.Companies making the transition topaperless can speed up the submissionand approval process by researchingpotential eTMF providers to ensurethat the systems they choose have beendesigned to align to both the letter andthe spirit of electronic filing regulations.

Act now – save time and money The urgent need for greater visibility intostudy conduct and the economic incentiveto speed up trial times are driving thepharma industry’s growing use of newtechnology.

Setting aside the staggering costs offailing to maximise sales opportunities asregulators set the bar higher for SOPcompliance and prepare their ownsystems for electronic submissions,the actual costs associated withmaintaining a paper-based clinicalTMF are steadily rising.

Early adopters of eTMF technologiesexperience greater inspection readiness,visibility, SOP compliance and costsavings from their eTMFs than thoseusing local or Cloud-file systems. AsCROs work to demonstrate their valueand keep their contracts, they have theopportunity to influence study design andprove their fees by helping sponsorseliminate excess secondary elements.

No matter what complex protocolssponsors put into place CROs, asobjective service providers, can helpsponsors move toward more efficient andeffective trial designs, and they will havethe data to demonstrate the risks of poortrial design.

CONTACTRik van Mol, Vice President, R&D StrategyVeeva SystemsEuropean head office Avinguda Diagonal 4202º 1ª C.P. 08037 Barcelona, SpainT +34 931 870 200UK office Marlow, BucksT +44 203 588 9500http://eu.veeva.com

“Standardising a commonnomenclature drives bettercommunication by harmonising thefiling efforts of diversestakeholders”

▼

freemantechnologypowder characterisation specialists

The FT4 Powder Rheometer® is the world’s most versatile instrument for measuring powder flow

properties and powder behaviour.

Understand how powder flow relates to tablet compression, mixing,

wet granulation end point and scale up, hopper flow,

DPI performance, segregation and much

more.

Visit our NEW website and download your copy of the recently released eBook

‘An Introduction to Powders’.

CONTACT UST: 44 (0) 1684 851 551F: 44 (0) 1684 851 552

E: info@freemantech.co.uk

www.freemantech.co.ukFreeman Technology Ltd, 1 Miller Court, Severn Drive, Tewkesbury, Gloucestershire, GL20 8DN, UK

045-048 mc1014 veeva_Layout 1 23/09/2014 12:45 Page 48