Premarketing clinical safety and PV activities, and the technology infrastructure that supports it, are typically outsourced to multiple contract research organisations (CROs) as part of their clinical trial programmes. **Disclaimer: This article was previously published. Sciformix is now a Covance company.

1. 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 that
supports it, are typically outsourced to
multiple contract research organisations
(CROs) as part of their clinical trial
programmes. Employing multiple CROs based
on how clinical programmes are managed
often leads to safety data being reported to
each clinical trial rather than at the product
level, and data are often collected in different
systems resulting in a lack of integration with
little or no control over data standardisation.
This puts organisations at risk at the time of
filing a marketing authorisation application
when it is important to review and analyse
consolidated data, define the initial product
label, and proactively identify and manage
safety concerns.
Further, for many small to medium
companies, having an internal resource-
heavy, end-to-end safety and risk
management system for marketed products
is not practical as it diverts extensive time,
effort and financial spend away from a
company’s core activities of product
development and marketing. Often, such
organisations do not have a distinct
established safety group and either the
clinical development or regulatory groups are
responsible for safety activities, leading to
lack of focus on critical PV activities.
The global regulatory landscape is now
stricter with increased expectations for
thorough clinical and safety documentation
and granular product information. Regulators
are also more stringent in their requirements
for timely and accurate reporting of adverse
events (AEs). There is heightened scrutiny of
AEs from sources beyond clinical trials and
spontaneous reports to call centres; including
non-interventional programmes, patient
assistance programmes and vendor
interaction with patients. As technology and
the ways in which patients interact and learn
more about their conditions and treatment
options evolve, there are additional
requirements and emphasis on safety data
obtained from social media and industry-
sponsored websites.
Establishing a comprehensive PV organisation
in-house can be challenging as dedicated and
experienced professionals are required to
manage both PV operations as well as the
enabling technology architecture/
infrastructure. On the technology side,
implementing validated, regulatory-compliant
PV systems requires significant investment in
robust quality management systems (QMSs)
and the right expertise to select, implement
and support the right solution(s). Yet, the
volume of the safety data is often relatively
low and volume surges highly unpredictable,
therefore not always justifying the
David Balderson
(david.balderson@sciformix.com)
is Vice President Global Safety
Operations. Throughout his
career, David has been a key
driver of major process
improvement initiatives,
leveraging technology to improve
efficiency wherever possible.
Prior to joining Sciformix, David
held senior leadership roles at
Amgen US, including Head of
Global Safety Operations and
Head of Global Regulatory
Operations. David spent 7 years in
Pharmacovigilance at GSK in the
UK. David holds a BSc in
Physiology and Pharmacology and
PhD in Neuroscience, both from
the University of Manchester, UK.
integrated safety and risk
management solutions –
addressing the needs of small
and medium-sized
biopharmaceutical companies
by David Balderson and Supriya Desai

2. PharmacoVigilance Revıew • Volume 9 Number 3 • 2017 5
expenditure. Similarly, on the functional side
of PV, responsibilities, such as aggregate
safety reporting, benefit–risk evaluation,
signal detection, case processing, and
management and development of risk
management plans, are becoming more
complex and resource ntensive. In Europe
and several other countries, specific
regulatory mandate to have a qualified
person (QP) responsible for PV (QPPV), and
local persons responsible for PV poses
additional operational challenges to the small
and medium-sized companies.
Small to medium-sized companies need to
rethink their current PV strategies and
embrace newer strategies to manage their PV
obligations which would allow them to focus
on their core clinical development objectives,
while staying compliant with the evolving PV
regulatory requirements for their marketed
product portfolio. Outsourcing of PV activities
can provide multiple benefits to
biopharmaceutical companies who can take
advantage of the expertise, systems and
flexibility available to complement current PV
activities within the company or provide an
entire dedicated team involved in end-to-end
PV activities, without additional burden of
hiring, training and retaining new staff.
Common regulatory and
safety-related pitfalls during
the product lifecycle
Figure 1 depicts several critical safety and
regulatory related activities that are part of
the product lifecycle, from preclinical
development through Phase IV. However,
smaller organisations are often unable to
prioritise these activities and may not have the
expertise or resources to undertake all
activities themselves. For many smaller
companies, not having a distinct PV
department with accountability for PV
activities rolling up into clinical development
or regulatory departments often impacts the
appropriate prioritisation of critical PV
activities.
Regulatory compliance may be compromised
if appropriate standard operating procedures
(SOPs) and working safety management
practices are not in place. Sub-optimal
processes and non-compliance issues can in
turn lead to higher costs, through missed
work, rework or low quality output1.
The most common pitfalls in safety
monitoring during the product lifecycle
include failure to:
l integrate multiple safety databases,
required for comprehensive safety review,
l develop robust written SOPs and work
instructions/practices for safety
management,
l analyse, review and document all pertinent
clinical safety data (AEs and events of
interest, laboratory data and other
investigations),
l review and update Investigator Brochure
(IB) on a timely basis,
l coordinate case submissions to regulators,
ethics committees and investigator sites
across multiple clinical studies, as required
and within timelines,
Supriya Desai, MD
(supriya.desai@sciformix.com) is
a Global Pharmacovigilance
Director with 18 years of
experience across clinical practice
and patient care, teaching and
various leadership roles in the
healthcare industry in clinical
development, medical writing,
pharmacovigilance and risk
management. In her current role
as Practice Head and Director of
Global Safety Practice at
Sciformix, she provides functional
and operational leadership to the
global pharmacovigilance team
(across India, Philippines and US)
involved in case processing and
medical review activities for
multiple clients across
pharmacovigilance, signal
management and allied safety
surveillance activities, spanning
diverse therapeutic areas.Figure 1: Critical safety and regulatory activities during the product lifecycle.

3. 6 PharmacoVigilance Revıew • Volume 9 Number 3 • 2017
l submit Development Safety Update
Report/Investigational New Drug Annual
Reports per schedule and applicable
regulations,
l ensure continuous audit and inspection
readiness at all times.
Outsourcing – key decision
drivers
There are three key areas of consideration
which determine and drive an organisation’s
decision process to outsource PV and
regulatory activities: namely people, process
and technology (see Figure 2).
The people factor
Work force limitations with respect to cost
and flexibility are an important consideration
for small to medium-sized organisations, and
external vendors can provide a flexible flow of
qualified, competent and specialised
personnel. Expertise across distinct work
streams, including safety, medical, regulatory
and technology, can be easily leveraged to get
the full range of expertise necessary for
meeting expected quality standards and
regulatory compliance. All of this is possible
without the need for the companies to
themselves recruit, train and retain new
dedicated staff.
Spikes and surges (both planned and
unplanned) are a reality in PV, and companies
need to be ready with a plethora of options to
handle different types of spikes (of varying
intensity and duration, see Figure 3). Working
with an outsourcing partner allows convenient
access to a broader pool of staff within the
outsourcing organisation. Resources can be
trained and deployed within weeks to manage
the increased workload (planned as well as
unplanned volume surges) and can then be
withdrawn as needed, providing flexible and
cost-effective resourcing solutions for surge
management.
Figure 2: Key Considerations for outsourcing PV and regulatory activities.

4. PharmacoVigilance Revıew • Volume 9 Number 3 • 2017 7
The process factor
Developing the right systems and processes to
support end-to-end PV activities is both a very
costly and laborious process. Specialty
outsourcing organisations can provide ready-
to-go, robust, tested and audited systems and
procedures, eliminating the time and expense
of starting from square one. These systems
and processes can be easily customised to the
company products and requirements. Further,
these processes are updated on an ongoing
basis to adapt to changing regulatory
requirements and technological advances.
The technology factor
Information technology is key to enabling a
robust safety and risk management
operation, and outsourcing vendors are able
to provide ready-to-go infrastructure and
technology services, and knowledgeable and
experienced technology staff. This ensures
strong business continuity and disaster
recovery plans.
Specialised vendors employ best-in-class
quality systems and oversight with well-
defined quality management plans, robust
service level agreement compliance
frameworks, and metrics, analytics and
reporting. Such vendors can help build
pragmatic and compliant systems to meet
company requirements in line with their
development, regulatory and commercial
strategy.
What is PV-in-a-Box?
Advantages and benefits
PV-in-a-Box (see Figure 4) is a holistic
customer-centric approach that brings
together safety, technology and advisory
services towards the provision of a complete
end-to-end PV solution by a single vendor for
the sponsor company. This integrated, flexible
and shared services outsourcing model
ensures regulatory compliance, guarentees
quality data (product safety), mitigates risks,
saves money, and allows the sponsor to focus
on what they do best – develop and deliver
new medicines to the market.
The effective combination of domain
expertise, agile processes and robust
technology results in high quality and
compliant operations, increased efficiency
and time savings. At the product level, PV-in-
a-Box allows real-time tracking of benefit–
risk profile and enables quicker and better
informed decisions on risk minimisation,
ultimately supporting maintenance of
efficacious and safer medicines in the
Figure 3: Companies need to be prepared for planned and unplanned spikes and dips, keeping
options open to take advantage of talent pools.

5. 8 PharmacoVigilance Revıew • Volume 9 Number 3 • 2017
market. An automated technology platform
(as part of the PV-in-a-Box solution) plays a
key role in effective PV management by
fostering collaboration between disparate
teams, enabling seamless processes and
effective analysis of safety data.
Conclusion
Both clinical trials and post-marketing
activities for pharmaceutical products
continue to grow in complexity and scope.
Furthermore, in this constantly evolving and
more stringent regulatory environment the
task of managing trials is more demanding
than ever. With this in mind, it is interesting
to note that while most of the industry's risk-
management efforts have focused on post-
marketing drug safety, the clinical trial
process holds a broad array of other
potential risks that could jeopardise a
company's product development investment,
including regulatory delays.
A common challenge across small and
medium-sized pharmaceutical companies is
how to create, develop and implement an
effective safety operation that can scale and
ensure regulatory compliance for their
growing product portfolio and case volumes.
Some companies need advice and direction
to get their safety operations started. While
others who have processes in place need
help 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 PV
activities from safety database implementation, to case processing and medical review, to safety
surveillance and risk management. It may include additional services, such as QPPV provision (for
products marketed in Europe), and call centre capabilities. By incorporating best-of-class processes,
technology and expertise, PV-in-a-Box ensures compliance and quality.

6. PharmacoVigilance Revıew • Volume 9 Number 3 • 2017 9
centre) to centralise and automate their
operations. Many desire a single vendor
strategy who utilise a holistic approach.
The increasingly stringent global regulatory
landscape means that it is necessary to
understand and regularly monitor a wide
range of safety data sources for updates.
Employing a comprehensive regulatory
intelligence framework and ensuring that
processes and SOPs are always compliant is
challenging, given the limited resources. The
final challenge is balancing high quality AE
processing and reporting against
unpredictable volumes while meeting new
needs in signalling, surveillance and risk
management.
Smart outsourcing depends on processes
with well-defined governance structure for
delivery of quality services coupled with a
long-term commitment to continuous
improvement by both the company and the
service provider. Partnering with a provider
who offers a scalable and business agile
solution with a suite of integrated products,
such as Sciformix’s PV-in-a-Box, will go a long
way in enabling sponsor companies to stay
ahead of the curve while staying compliant
with regulatory requirements and help with
optimal benefit–risk evaluation of their
products.
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 (Accessed
23 January 2017).
2 European Medicines Agency. Guideline on Good
Pharmacovigilance Practices (GPV). London, UK: EMA;
2016. Available at:
http://www.ema.europa.eu/docs/en_GB/document_li
brary/Scientific_guideline/2016/08/WC500211728.pdf
(Accessed 24 January 2017).
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Clinical
Research
Manual
Editors
David Luscombe
Peter D Stonier
2013 Edition