Drug safety has moved into the media spotlight and now more
than ever it is essential that patient safety is seen to be of utmost
importance to regulators as well as pharmaceutical companies. Outsourcing in the pharmaceutical market has
grown vastly over the last 10 years, with PV market estimated to reach $5billion
in 2019, at a Compound Annual Growth Rate (CAGR) of 12.9% from 2013 to 2019.It
has become almost standard practice among multinational companies to develop
global sourcing programs. The outsourcing of pharmacovigilance tasks provides a
flexible solution to the ever changing demands of running a specialist
pharmacovigilance team. Duties usually be performed in-house are contracted to
a dedicated service provider, whether it is on a full service, partial or
project basis. The trend seen in drug safety services has largely paralleled
the trends seen in the clinical research and product development services.
When Outsourcing
helps?
·
When we need to have short term additional resources.
·
When we need to have readymade troop of skilled and trained
resources.
·
When we need the
flexibility to respond to varying workloads.
·
Outsourcing
approach of ‘pay as you go’ allows you to respond fully to regulatory
obligations, without the need of retaining a full pharmacovigilance team on the
payroll.
·
The benefits of outsourcing include reduced costs due to less
effort needed for staff recruitment, management and training. With stricter
regulatory requirements, the hiring of experienced safety personnel has become
highly competitive.
What services can be outsourced?
Company size, the size of the pharmacovigilance department
and existing license or development partnerships influence outsourcing
decisions. It is possible to outsource an entire pharmacovigilance (end to end)
or medical information department or just individual elements, depending on
your requirements.
Recent Trends?
The range of
contracted services is determined by the type of safety service providers,
including individual consultants, specialty Clinical Research Organizations
(CROs), large, full-service CROs and global service providers under the
umbrella of business process outsourcing (BPO). Life science companies, CRO’s,
KPO’s, and BPO’s shifted for doing this business. These companies come up with robust
technology and mature processes to effectively address risks and concerns
associated with delegating responsibility to service providers. The
negotiations between the pharmaceutical company and the regulatory authorities
on the risk management program had been unsuccessful over several years so the
pressure has increased of late, in order to comply with evolving regulations
worldwide. Regulatory observation along the entire product life cycle has seen a
substantial increase, with all areas of the business being affected.
Examples of
outsourcing consultation trends include:
·
Full PV service outsourcing (ICSR
management & reporting of cases).
a. Small biotech
companies typically have no drug safety department and routinely
Outsource all safety services including the safety database.
b. Mid-sized pharma
companies generally have the knowledge and resources to cater
to the demands of the global pharmacovigilance environment. They face
challenges to meet fluctuating resource needs associated with a changing product
development.
c. Large pharma
companies have comprehensive expert pharmacovigilance
departments with global infrastructure and databases.
·
Case processing (Regulators requested
an active surveillance study to detect
rare and serious
adverse events for risk minimization).
·
Literature screening (Usually provide
flexible end-to-end literature search and review solutions that assist
companies and individuals to meet their regulatory goals).
a. Literature review
help users to stay updated in their research.
b. Provides complete
picture of today’s global clinical research in clinical medicine which is
enabled by broad coverage with numerous access point, extensive search
capabilities and coverage of immense data.
c. Save research time
by providing one source for variety of research data including abstracts,
author’s name, contact details and information per bibliographic record than in
other resources.
·
Signal detection/ benefits risk
assessment (Contracted experts are external, they can provide an unbiased view,
may have special value in decision making process involved in signal detection
and risk management activities required for the drug.
·
MedDRA coding and writing risk
management plans.
·
Aggregate reporting(PSURs/PADERs/PBRERs/DSURs)
a.
Periodic benefit/risk evaluation
reports (PBRERs)
b.
Periodic safety update reports
(PSURs)
c.
Periodic adverse drug experience
reports (PADERs)
d.
Summary bridging reports
e.
Developmental safety update reports
(DSURs)
f.
Pharmacovigilance risk assessment
committee (PRAC) responses/health authority responses.
·
Aggregate reports may include
following contents:
a.
Introduction
b.
Worldwide market authorisation status
(dates of MAH, limits on indications if relevant to safety , treatment
indications and special populations covered by the market authorisation, lack
of approval, including explanation, by regulatory authorities, trade name(s), withdrawal
by the company of a licence application submission if related to safety or efficacy,
dates of launch when known.
c.
Update of regulatory authority (MAH
actions taken for safety issues). The safety related reasons that led to these
actions should be described and documentation appended when appropriate; any
communication with the health profession (e.g., Dear physician letters) as a
result of such action should also be described with copies appended.
d.
Changes to the RSI’s (reference
safety information). It should be numbered, dated and appended to the PSUR and
include the date of last revision. The revised labelling document should be
used as the reference for the next report and the next period.
e.
Patient exposure (An estimation of
accurate patient exposure should cover the same period as
the interim safety data).
f.
Presentation of individual case
histories: Case presented as line listing, the line listing(s) should include
each patient only once regardless of how many adverse event/reaction terms are
reported for the case. If there is more than one event/reaction, they should
all be mentioned but the case should be listed under the most serious ADR
(sign, symptom or diagnosis), as judged by the MAH. An aggregate summary for
each of the line listings should usually be presented.
g.
MAH’s Analysis of Individual Case
Histories: This section may be used for brief comments on the data concerning
individual cases. Discussions can include: serious or unanticipated findings
(their nature, medical significance, mechanism, reporting frequency, etc.). The
focus here should be on individual case discussion and should not be confused
with the global assessment in the overall Safety Evaluation.
h.
Studies: All completed studies
(non-clinical, clinical, and epidemiological) yielding safety information with
potential impact on product information, studies specifically planned or in
progress, and published studies that address safety issues, should be
discussed.
i.
Overall safety information: A change
in characteristics of listed reactions, e.g. severity, outcome, target
population. Serious unlisted reactions, Non-Serious unlisted reactions. An
increased reporting frequency of listed reactions. Drug
abuse/misuse/overdose/interactions. Pregnancy, breastfeeding related safety
concerns. Effects on vulnerable patients.
j.
Conclusion: indicate which safety
data do not remain in accord with the previous cumulative
experience, and with the reference
safety information (CCSI), specify and justify any action recommended or
initiated.
·
Electronic reporting set up (By E2B
format).
·
Contractual agreement production and
maintenance
·
Risk management planning and
services.
·
Due diligence support activities (The
due diligence should be supplemented with data on the tenure of the staff and
management team).
·
Provide insight and overview of
global regulations.
·
PV Training (The sponsor drug safety
team provided initial training to the CRO staff at the beginning of the
relationship, the CRO is responsible for training new staff (train-the-trainer
principle).
·
Quality compliance training and
review (Reducing costs through low-cost or off-shore outsourcing results in
quality issues and regulatory non-compliance and deviations. It is pertinent to
maintain the necessary oversight and engagement with the outsourcing partners
or the vendors).
·
Audit and inspection readiness and
preparation. (A track record of regulatory compliance and low non-conformity
rates usually indicates a robust quality management system. Audits during the
cooperation either by in-house staff or an external auditor are the best tools
to reconfirm that the provider meets quality standards and implements
adjustments in a changed regulatory environment.
·
Clinical safety assessment (Whether
you are seeking an experienced QPPV (Qualified Person) service only, LPVRP (Local
Pharmacovigilance Responsible Person) service, report writing services or an
entire team, service providers are able to provide subject matter expertise for
matters pertaining to complex global pharmacovigilance and Medical Information
regulations, expertise which may not be readily available in house). Most
countries have requirement of LPVRP/QPPV. If you are exporting your drugs to
any international market, it is critical to have their respective supports. Regulators
prefer dealing with senior professionals experienced in pharmacovigilance. Regulators
prefer having a single point of contact to address their queries and concerns. It
is helpful if these are in charge of the entire pharmacovigilance operations in
their region. Should be 24×7 available. The role of QPPV and/or the deputy can
be outsourced, however this must form part of a formal agreement which will
have clear definitions of the responsibilities of each party, moreover
confidentiality must be maintained.
·
A QPPV has a central role focused on
ensuring the company is meeting all of its PV responsibilities and ultimately
the safety of the public using the medicine is maximised.
·
Labelling documents/ RSI’s Updating
revision (CCDS/CCSI/PIL/SPC assessments)
·
SOP writing/updating/ Training (SOPs
are important and can impact cost, adherence to the
sponsor’s SOPs can
be advantageous. Sponsor’s SOPs, user manual and entry/coding conventions).
Conclusion:
Outsourcing pharmacovigilance activities is a standard
business practice in a rapidly expanding market segment. It can be successful
provided:
a.
The service
provider has the qualification for the pharmacovigilance services.
b.
Contractual
agreement includes well defined responsibilities.
c.
Transparency
maintained at project start.
References:
2.
Report to the European
Commission on Pharmacovigilance audits carried out in the Irish Medicines Board
in Ireland from 21-SEP- 2012 to 20-SEP-2013 retrieved from
5.
http://www.pharmabio.qc.ca/content/documents/pdf/R%C3%A9f.Comp%C3%A9tences%20Anglais/Pharmacovigilance%20Specialist.pdf
