integrated safety and risk management solutions

4 PharmacoVigilance Revıew • Volume 9 Number 3 • 2017

Akey issue for small and medium-

sized enterprises (SMEs) is the

optimal utilisation of their

limited resources to move their product

pipeline through clinical development,

and launching and marketing their

approved product(s). Often, these

organisations are not able to prioritise

safety and risk management activities

and may not have the expertise to

undertake all the required activities

themselves. Not having a distinct

pharmacovigilance (PV) department

with accountability for PV activities

rolling up into clinical development or

regulatory departments often impacts

the appropriate prioritisation of critical

PV activities.

Premarketing clinical safety and PV activities,and the technology infrastructure thatsupports it, are typically outsourced tomultiple contract research organisations(CROs) as part of their clinical trialprogrammes. Employing multiple CROs basedon how clinical programmes are managedoften leads to safety data being reported toeach clinical trial rather than at the productlevel, and data are often collected in differentsystems resulting in a lack of integration withlittle or no control over data standardisation.This puts organisations at risk at the time offiling a marketing authorisation applicationwhen it is important to review and analyseconsolidated data, define the initial productlabel, and proactively identify and managesafety concerns.

Further, for many small to mediumcompanies, having an internal resource-heavy, end-to-end safety and risk

management system for marketed productsis not practical as it diverts extensive time,effort and financial spend away from acompany’s core activities of productdevelopment and marketing. Often, suchorganisations do not have a distinctestablished safety group and either theclinical development or regulatory groups areresponsible for safety activities, leading tolack of focus on critical PV activities.

The global regulatory landscape is nowstricter with increased expectations forthorough clinical and safety documentationand granular product information. Regulatorsare also more stringent in their requirementsfor timely and accurate reporting of adverseevents (AEs). There is heightened scrutiny ofAEs from sources beyond clinical trials andspontaneous reports to call centres; includingnon-interventional programmes, patientassistance programmes and vendorinteraction with patients. As technology andthe ways in which patients interact and learnmore about their conditions and treatmentoptions evolve, there are additionalrequirements and emphasis on safety dataobtained from social media and industry-sponsored websites.

Establishing a comprehensive PV organisationin-house can be challenging as dedicated andexperienced professionals are required tomanage both PV operations as well as theenabling technology architecture/infrastructure. On the technology side,implementing validated, regulatory-compliantPV systems requires significant investment inrobust quality management systems (QMSs)and the right expertise to select, implementand support the right solution(s). Yet, thevolume of the safety data is often relativelylow and volume surges highly unpredictable,therefore not always justifying the

David Balderson([email protected])is Vice President Global SafetyOperations. Throughout hiscareer, David has been a keydriver of major processimprovement initiatives,leveraging technology to improveefficiency wherever possible.Prior to joining Sciformix, Davidheld senior leadership roles atAmgen US, including Head ofGlobal Safety Operations andHead of Global RegulatoryOperations. David spent 7 years inPharmacovigilance at GSK in theUK. David holds a BSc inPhysiology and Pharmacology andPhD in Neuroscience, both fromthe University of Manchester, UK.

integrated safety and riskmanagement solutions –addressing the needs of smalland medium-sizedbiopharmaceutical companiesby David Balderson and Supriya Desai

PharmacoVigilance Revıew • Volume 9 Number 3 • 2017 5

expenditure. Similarly, on the functional sideof PV, responsibilities, such as aggregatesafety reporting, benefit–risk evaluation,signal detection, case processing, andmanagement and development of riskmanagement plans, are becoming morecomplex and resource ntensive. In Europeand several other countries, specificregulatory mandate to have a qualifiedperson (QP) responsible for PV (QPPV), andlocal persons responsible for PV posesadditional operational challenges to the smalland medium-sized companies.

Small to medium-sized companies need torethink their current PV strategies andembrace newer strategies to manage their PVobligations which would allow them to focuson their core clinical development objectives,while staying compliant with the evolving PVregulatory requirements for their marketedproduct portfolio. Outsourcing of PV activitiescan provide multiple benefits tobiopharmaceutical companies who can takeadvantage of the expertise, systems andflexibility available to complement current PVactivities within the company or provide anentire dedicated team involved in end-to-endPV activities, without additional burden ofhiring, training and retaining new staff.

Common regulatory andsafety-related pitfalls duringthe product lifecycle Figure 1 depicts several critical safety andregulatory related activities that are part ofthe product lifecycle, from preclinicaldevelopment through Phase IV. However,

smaller organisations are often unable toprioritise these activities and may not have theexpertise or resources to undertake allactivities themselves. For many smallercompanies, not having a distinct PVdepartment with accountability for PVactivities rolling up into clinical developmentor regulatory departments often impacts theappropriate prioritisation of critical PVactivities.

Regulatory compliance may be compromisedif appropriate standard operating procedures(SOPs) and working safety managementpractices are not in place. Sub-optimalprocesses and non-compliance issues can inturn lead to higher costs, through missedwork, rework or low quality output1. The most common pitfalls in safetymonitoring during the product lifecycleinclude failure to:

l integrate multiple safety databases,required for comprehensive safety review,

l develop robust written SOPs and workinstructions/practices for safetymanagement,

l analyse, review and document all pertinentclinical safety data (AEs and events ofinterest, laboratory data and otherinvestigations),

l review and update Investigator Brochure(IB) on a timely basis,

l coordinate case submissions to regulators,ethics committees and investigator sitesacross multiple clinical studies, as requiredand within timelines,

Supriya Desai, MD([email protected]) isa Global PharmacovigilanceDirector with 18 years ofexperience across clinical practiceand patient care, teaching andvarious leadership roles in thehealthcare industry in clinicaldevelopment, medical writing,pharmacovigilance and riskmanagement. In her current roleas Practice Head and Director ofGlobal Safety Practice atSciformix, she provides functionaland operational leadership to theglobal pharmacovigilance team(across India, Philippines and US)involved in case processing andmedical review activities formultiple clients acrosspharmacovigilance, signalmanagement and allied safetysurveillance activities, spanningdiverse therapeutic areas. Figure 1: Critical safety and regulatory activities during the product lifecycle.


l submit Development Safety UpdateReport/Investigational New Drug AnnualReports per schedule and applicableregulations,

l ensure continuous audit and inspectionreadiness at all times.

Outsourcing – key decisiondriversThere are three key areas of considerationwhich determine and drive an organisation’sdecision process to outsource PV andregulatory activities: namely people, processand technology (see Figure 2).

The people factorWork force limitations with respect to costand flexibility are an important considerationfor small to medium-sized organisations, andexternal vendors can provide a flexible flow ofqualified, competent and specialisedpersonnel. Expertise across distinct work

streams, including safety, medical, regulatoryand technology, can be easily leveraged to getthe full range of expertise necessary formeeting expected quality standards andregulatory compliance. All of this is possiblewithout the need for the companies tothemselves recruit, train and retain newdedicated staff.

Spikes and surges (both planned andunplanned) are a reality in PV, and companiesneed to be ready with a plethora of options tohandle different types of spikes (of varyingintensity and duration, see Figure 3). Workingwith an outsourcing partner allows convenientaccess to a broader pool of staff within theoutsourcing organisation. Resources can betrained and deployed within weeks to managethe increased workload (planned as well asunplanned volume surges) and can then bewithdrawn as needed, providing flexible andcost-effective resourcing solutions for surgemanagement.

Figure 2: Key Considerations for outsourcing PV and regulatory activities.


The process factor Developing the right systems and processes tosupport end-to-end PV activities is both a verycostly and laborious process. Specialtyoutsourcing organisations can provide ready-to-go, robust, tested and audited systems andprocedures, eliminating the time and expenseof starting from square one. These systemsand processes can be easily customised to thecompany products and requirements. Further,these processes are updated on an ongoingbasis to adapt to changing regulatoryrequirements and technological advances.

The technology factorInformation technology is key to enabling arobust safety and risk managementoperation, and outsourcing vendors are ableto provide ready-to-go infrastructure andtechnology services, and knowledgeable andexperienced technology staff. This ensuresstrong business continuity and disasterrecovery plans.

Specialised vendors employ best-in-classquality systems and oversight with well-defined quality management plans, robustservice level agreement complianceframeworks, and metrics, analytics andreporting. Such vendors can help build

pragmatic and compliant systems to meetcompany requirements in line with theirdevelopment, regulatory and commercialstrategy.

What is PV-in-a-Box?Advantages and benefitsPV-in-a-Box (see Figure 4) is a holisticcustomer-centric approach that bringstogether safety, technology and advisoryservices towards the provision of a completeend-to-end PV solution by a single vendor forthe sponsor company. This integrated, flexibleand shared services outsourcing modelensures regulatory compliance, guarenteesquality data (product safety), mitigates risks,saves money, and allows the sponsor to focuson what they do best – develop and delivernew medicines to the market.

The effective combination of domainexpertise, agile processes and robusttechnology results in high quality andcompliant operations, increased efficiencyand time savings. At the product level, PV-in-a-Box allows real-time tracking of benefit–risk profile and enables quicker and betterinformed decisions on risk minimisation,ultimately supporting maintenance ofefficacious and safer medicines in the

Figure 3: Companies need to be prepared for planned and unplanned spikes and dips, keepingoptions open to take advantage of talent pools.


market. An automated technology platform(as part of the PV-in-a-Box solution) plays akey role in effective PV management byfostering collaboration between disparateteams, enabling seamless processes andeffective analysis of safety data.

Conclusion Both clinical trials and post-marketingactivities for pharmaceutical productscontinue to grow in complexity and scope.Furthermore, in this constantly evolving andmore stringent regulatory environment thetask of managing trials is more demandingthan ever. With this in mind, it is interestingto note that while most of the industry's risk-management efforts have focused on post-

marketing drug safety, the clinical trialprocess holds a broad array of otherpotential risks that could jeopardise acompany's product development investment,including regulatory delays.

A common challenge across small andmedium-sized pharmaceutical companies ishow to create, develop and implement aneffective safety operation that can scale andensure regulatory compliance for theirgrowing product portfolio and case volumes.Some companies need advice and directionto get their safety operations started. Whileothers who have processes in place needhelp selecting and maintaining technology(safety database) and services (medical call

Figure 4: PV-in-a-Box is an integrated PV-shared services model, encompassing end-to-end PVactivities from safety database implementation, to case processing and medical review, to safetysurveillance and risk management. It may include additional services, such as QPPV provision (forproducts marketed in Europe), and call centre capabilities. By incorporating best-of-class processes,technology and expertise, PV-in-a-Box ensures compliance and quality.


centre) to centralise and automate theiroperations. Many desire a single vendorstrategy who utilise a holistic approach.

The increasingly stringent global regulatorylandscape means that it is necessary tounderstand and regularly monitor a widerange of safety data sources for updates.Employing a comprehensive regulatoryintelligence framework and ensuring thatprocesses and SOPs are always compliant ischallenging, given the limited resources. Thefinal challenge is balancing high quality AEprocessing and reporting againstunpredictable volumes while meeting newneeds in signalling, surveillance and riskmanagement.

Smart outsourcing depends on processeswith well-defined governance structure fordelivery of quality services coupled with along-term commitment to continuous

improvement by both the company and theservice provider. Partnering with a providerwho offers a scalable and business agilesolution with a suite of integrated products,such as Sciformix’s PV-in-a-Box, will go a longway in enabling sponsor companies to stayahead of the curve while staying compliantwith regulatory requirements and help withoptimal benefit–risk evaluation of theirproducts.

References 1 Deloitte. Pharmacovigilance (PV) Outsourcing –

Emerging PV Business Models. New York City, NY,USA: Deloitte; 2014. Available at:https://www2.deloitte.com/content/dam/Deloitte/us/Documents/life-sciences-health-care/us-lshc-pharmacovigilance-outsourcing-021115.pdf (Accessed23 January 2017).

2 European Medicines Agency. Guideline on GoodPharmacovigilance Practices (GPV). London, UK: EMA;2016. Available at:http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/08/WC500211728.pdf(Accessed 24 January 2017).

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ClinicalResearchManual

Editors

David Luscombe

Peter D Stonier

2013 Edition

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