BRUSSELS 2014 HIGHLIGHTS

ISSUE 02
BRINGING YOU UPDATES FROM THE LATEST
DRUG SAFETY, RISK MANAGEMENT AND
PHARMACOVIGILANCE MEETINGS
BRUSSELS 2014
HIGHLIGHTS
INSIDE THIS ISSUE
MINIMISING SAFETY RISKS
BIOLOGICS CHANGING
THE PV LANDSCAPE
PUBLIC PARTICIPATION IN PV
IS THE NEW PV LEGISLATION
DELIVERING?
OUTSOURCING PV:
A SUCCESS STORY
DEALING WITH BIG DATA
SOCIAL MEDIA IN SIGNAL
DETECTION
THE KEY ROLE OF THE
PSMF IN INSPECTIONS
SAFETY
REPORTS
IS THE NEW PV LEGISLATION DELIVERING
ON THE SET OBJECTIVES?
Sue Rees (EU QPPV, Amgen) argued that while some of the objectives set
out by the EMA for the new PV regulations have been met, others fall short of
reaching the set goals, revealing the evolutionary nature of this PV legislation.
Sue Rees observed that some of the benefits to the pharmaceutical industry of
the 2012 legislation/GVP modules include:
1) a big step towards an EU-based PV and product evaluation;
2)an increased oversight of the PV system via the pharmacovigilance
system master file (PSMF), including definitions of the roles of the EU
QPPV and senior management;
3)the advent of periodic benefit-risk evaluation reports (PBRERs), including
acceptance of their format and a harmonisation under ICH – raising the
focus on signal evaluation rather than on single case reports (ICSRs);
WELCOME TO THE
PHARMACOVIGILANCE, DRUG
SAFETY AND RISK MANAGEMENT
MEETING HIGHLIGHTS
The Pharmacovigilance, Drug
Safety and Risk Management
meeting held in Brussels on 26–27
November 2014 focused on the
major topic of discussion over the
last two years in pharmacovigilance
(PV): how to interpret and
implement the new European 2012
PV legislation. This legislation was
ultimately set in place to achieve
continuous benefit/risk analysis of
marketed medicines throughout
their lifecycle, with constant
monitoring and improvement of PV
processes resulting in an enhanced
quality of safety monitoring.
Increased and open communication
and thus transparency to patients,
healthcare providers and regulatory
agencies should increase patient
safety further.
PUBLIC PARTICIPATION IN PV
The Good Pharmacovigilance
Practices (GVP) modules XI and
XII have not yet been released.
They are sure, however, to spark
some additional communication
activities from marketing
authorisation holders (MAHs)
as they will be key in describing
guidelines for the communication
of PV-related information to the
public. Susanna Palkonen (CEO,
EFA) shared the information that
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already, as a result of opening of
patient reporting of adverse drug
reactions (ADRs) to the European
Medicines Agency (EMA), there
has been a 60% increase over the
past year in ADR reporting from
15,000 ADRs to 25,000 ADRs.
This increased reporting has in
turn led to changes in drug safety
information. The EMA has directed
that patients must have access
to information at all points of the
benefit/risk process, including
membership in advisory boards,
committees (Pharmacovigilance
Risk Assessment Committee
[PRAC], Committee for Medicinal
Products for Human Use [CHMP]),
etc. Important issues to address
in the future will be how to best
communicate with all patient
groups, including patients from
underprivileged backgrounds where
health literacy may be a challenge.
4)more detailed guidance of the MAHs compared to the previous Volume
9A EMA Guideline. One distinct benefit is the increased interaction and
communication between regulators and company representatives,
allowing an open dialogue in the mutual interest of optimisation of the
PV systems and improved patient safety. Thus, a new dialogue forum
for industry, the EMA and the PRAC has been established in 2014 with
quarterly meetings commencing in May 2014.
Although a good tool for providing
clarity, the PSMF has also been
and remains significant additional
work for companies to set up and
keep updated. Further challenges
included the implementation of
new processes and formats for risk
management plans (RMPs) and
PBRERs. Moreover, the expected
simplification of the ICSR reporting
procedure is now only anticipated
to be implemented by Q4 2015.
Finally, the delay in release of some
of the GVP modules necessitates
companies to readjust the PSMF
and associated SOPs repeatedly,
following the release and added
requirements of new GVP modules.
INCREASED OPEN DIALOGUE
BETWEEN REGULATORS AND
COMPANY REPRESENTATIVES
IS A KEY BENEFIT OF THE
2012 LEGISLATION
"
MINIMISING SAFETY RISKS
The new risk management plan
format suggested for use in Europe
in the context of GVP module V has
been globally accepted. However, the
tabulated format for risk reporting
which was aimed to allow for succinct
documents has in many, if not most,
instances turned into page-long
text boxes for each table row, thus
defeating the original objective. When
preparing RMPs in companies with a
large portfolio, Phillip Eichorn (WW
Safety and Regulatory, Pfizer) pointed
to the advantage of using a portfoliowide rather than product-based
approach. This will aid consistency
across products for AE handling, risk
minimisation, and other activities.
Risk minimisation strategies and
activities, and measures of their
effectiveness, were the topics of
several presentations and discussions
(Miguel Arguinzoniz, Drug Safety and
Risk Management, Roche-Genentech;
Philippe Close, EU QPPV Novartis),
including a round-table discussion
under the guidance of John Solomon
(Head of PV, Sanofi UK). The GVP
module XVI released in mid 2014
presents a variety of tools and
suggestions; however, the actual and
reasonable implementation of these
tools is still to be achieved. Again, a
risk-based approach is advocated:
evaluate the severity and frequency
of identified risks, rank them
according to impact, and prioritise risk
minimisation measures accordingly.
When designing a programme for
risk minimisation, it is important
to simultaneously elaborate the
method intended for measurement
of effectiveness to ensure optimal
feasibility of both.
Previously, monitoring of the
effectiveness of enhanced risk
minimisation activities (RMAs) might
primarily have been requested by
regulatory authorities, but now
there is an increasing trend towards
requests for additional effectiveness
measures of routine RMAs. These
may, for example, aim at assessing
that warnings and precautions listed
in the label are indeed being read,
understood and implemented by
HCPs and/or patients.
A RISK MINIMISATION
PROGRAMME SHOULD
BE DEVELOPED WITH
ITS METHOD OF
MEASUREMENT
"
SAFETY REPORTS ISSUE 02
p. 03
SAFETY
REPORTS
BIOLOGICS AND BIOSIMILARS ARE
CHANGING THE PV LANDSCAPE
SOCIAL MEDIA IN SIGNAL DETECTION:
WEB-RADR
One of the core tasks of MAH safety
teams remains the detection and
evaluation of new safety signals. The
manual triage of all reports of ADRs
is gradually being taken over by
automated/semi-automated systems.
With proper data-filtering tools, such
systems will allow the bulk of nonrelevant, non-serious ADRs to be
described by staff with a more basic
knowledge background, whereas
serious ADRs may be subject to
scrutiny by safety physicians for
evaluation of the occurrence of
potential new safety signals. In the
end, this may translate into increased
efficiency as well as increased quality
and time available for the important
ADRs to be evaluated.
MANY THOUSANDS OF
TWEETS OR SIMILAR
MESSAGES MAY
DESCRIBE NEGATIVE
EFFECTS OF A MEDICINAL
PRODUCT
"
This, of course, is relevant not least
for information posted on the internet
via social media. Many thousands
or even millions of tweets or similar
messages are posted on an annual
basis, some of which may describe
negative effects of a medicinal
product. How should the tweets
be interpreted and evaluated in
the context of signal detection?
This is one of the research topics
of a recently started 3-year project
named ‘WEB-RADR’, which is led by a
consortium of industry and regulatory
agencies including the UK’s Medicines
and Healthcare Products Regulatory
Agency (Phil Tregunno, MHRA). The
WEB-RADR project aims to develop
a mobile app to allow healthcare
professionals and the public to report
suspected ADRs to national European
regulators and, furthermore, wishes to
investigate the potential for publicly
available social media data (e.g.
tweets) to be used for identifying
drug safety issues. Algorithms will be
established to create an automated
filtering of the tweet information to
yield potentially useful information.
READY FOR INSPECTION?
THE IMPORTANCE OF THE PSMF
In anticipation of the release in
2015 of the GVP guidance module
chapter PII concerning PV for
biomedical medicinal products, a
presentation by Violetta Kyburz
(Commercial Director, Fishawack
Archimed) provided insights into
the PV-related issues of biologics
and biosimilars compared with
small molecule pharmaceuticals.
Biologics and biosimilars are here
to stay with currently 7 out of the
top 10 bestselling drugs being
biologic compounds. There are
major differences in their preclinical development, including
the challenge of developing a
stable manufacturing process. The
challenges in manufacturing-related
variability of these complex entities
include aggregation and batch-tobatch variability.
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VARIATIONS IN THE
MANUFACTURING
PROCESS OF BIOLOGICS
MAY SIGNIFICANTLY
IMPACT SAFETY
"
Biosimilars often start production
with a different cell line and a
different up- and downstream
manufacturing process, so they are
similar to the reference biologic, but
may be different with respect to
molecular structure, glycosylation
and other characteristics. This may
affect both efficacy and safety.
Such variations may significantly
impact PV (benefit/risk) and require
even more careful monitoring.
Biologics and biosimilars are
frequently designated orphan
drugs with reduced demands preauthorisation regarding patient
numbers to be included in pivotal
studies. To compensate for the
lack of data collected pre-launch,
recently approved biosimilars have
all had to meet added requirements
specified by regulatory authorities
in terms of post-authorisation
safety/efficacy studies (PASS/
PAES) and registries to ascertain
whether safety and benefit profiles
have an acceptable and positive
balance.
Abbott) and also discussed in one
of the seven round-table sessions
which were a fruitful and interactive
part of the meeting.
Central to the improved organisation
of safety monitoring is the PSMF,
which allows PV processes to
be described and actions to be
documented in a comprehensive
and systematic manner. As it is such
a central document, it was presented
in detail by Monika Manske
(Assistant Director PV Compliance,
The PSMF and the corresponding
completeness of an MAH’s PV
system are the main focus of
attention for pharmacovigilance
inspectors. Inspection findings
particularly relate to GVP Modules
I, II and III and have, for example
in Belgium as explained by Nele
Matthijs (PV inspector, FAGG),
revealed some of the difficulties
in achieving a complete and
continuously updated PSMF (GVP
Module II). Many suggestions for
achieving inspection readiness
were presented, including that
audit findings should immediately
be presented in the PSMF as well
as vendor audit plans and any PV
agreements in place. On the positive
side, the inspectors are apparently
also observing a definite positive
trend towards improved quality
of PV management in inspected
companies, which translates into
improvement in patient safety.
Key for achieving good quality is
communication, awareness and
structured planning and training
across the MAH organisation.
INSPECTORS ARE
OBSERVING A
DEFINITE POSITIVE
TREND TOWARDS
IMPROVED QUALITY
OF PV MANAGEMENT
"
SAFETY REPORTS ISSUE 02
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SAFETY
REPORTS
OUTSOURCING PHARMACOVIGILANCE:
A SUCCESS STORY
NEEDLES IN HAYSTACKS:
DEALING WITH INCREASING
AMOUNTS OF DATA
Automated systems are increasingly
being employed for literature
screening. This is another field where
volumes of data are growing, causing
safety teams to spend too much time
screening the literature rather than
focusing on the publications with
relevant cases in terms of potential
signals. In collaboration with MAHs,
a system has been developed (Mark
Drinkwater, Proquest) to deliver
the potentially relevant publications
by searching the medical literature
databases available (e.g. Embase,
Medline, Derwent, and Biosis) using
carefully designed and agreed sets of
search terms.
With the changes that have
occurred in pharmacovigilance over
the past few years, both in terms
of legislation and volume of work,
there are expanding requirements
for MAHs and therefore new
opportunities for outsourcing to
vendors, explained Irina Bogatyreva
(Director, Safety Physician, UCB).
There are many questions to ask
when considering outsourcing
pharmacovigilance tasks as there
are with any outsourcing project and
several key ones are shown in the
box below.
✔What are you trying to
accomplish?
✔Which areas or functions would
you outsource?
✔How much ownership would you
like to have?
✔What is the expected lifetime of
the partnership?
✔Do you anticipate the scope of the
outsourcing evolving?
Once UCB had decided that they
wanted to explore the outsourcing
route, they considered many
vendors, issued RFPs, and had
proposal negotiations. The company
was looking for a seasoned vendor
with a demonstrated track record
and organic growth, detailed
knowledge of pharmacovigilance
regulations, a significant headcount,
high ethical standards and a good
reputation, as well as processes that
promoted high quality.
After UCB had chosen their partner,
they undertook a pilot project
followed by an approach of slow
transition as there were challenges
to be overcome, such as building
data access for the vendor without
compromising the security of the
company’s IT system. In addition,
UCB has a portfolio of around 170
pharmaceuticals across several
therapy areas so full, immediate
transition would have been a highrisk approach.
WITH A GOOD PV PARTNER
IN PLACE, THE UCB TEAM
COULD FOCUS MORE
EFFECTIVELY ON CORE
STRATEGIC ACTIVITIES
"
A SWOT analysis of the partnership
after two years demonstrated
that the project was a success,
with their objectives successfully
met. In particular, the UCB
Pharmacovigilance Team was able
to focus more effectively on core
strategic activities, and a flexible,
high-quality staffing solution was in
place to respond to future growth
in pharmacovigilance work.
This newsletter has been prepared
independently by Fishawack
Archimed following attendance at the
meeting and using the slides made
available to all delegates afterwards.
The opinions expressed are not
necessarily those of the organisers or
the presenters.
© 2014 Fishawack Archimed AG
THE ADDED VALUE OF
SAFETY INFORMATION
FROM PATIENT SUPPORT
AND MARKET RESEARCH
PROGRAMMES IS
QUESTIONABLE
"
Data derived from patient support
programmes (PSPs) and market
research programmes (MRPs) are
other large sources of more or less
complete information which have
been examined for relevance in terms
of identifying potential new safety
signals. In an analysis conducted
by Genentech (Elaine Chan, US
Drug Safety, Genentech), ADR
reports from PSPs and MRPs were
Fishawack Archimed AG
Fishawack Archimed is the drug
safety and pharmacovigilance support
division of the Fishawack Group of
Companies. Established in 1997 in
Zofingen, Switzerland, Fishawack
Archimed has developed into a
specialist provider of drug safety
and regulatory communications,
including pharmacovigilance
support, for leading pharmaceutical,
biotechnology and medical device
companies.
evaluated retrospectively (1.2 million
ADRs) and prospectively (700,000
ADRs). Following evaluation for
completeness, it was found that ADR
reports from PSPs had a markedly
higher level of completeness
than MRP-derived ADR reports.
Overall, however, there was sparse
information available in the reports.
More than 40,000 evaluable ADR
reports were then used to re-evaluate
the benefit/risk profile for all 22
medicinal products implicated in the
PSPs or MRPs with the result that
none of the benefit/risk profiles were
found to have changed. Using a riskbased approach, the added value
of including the safety information
gathered in the context of PSPs and
MRPs was questioned.
The team at Fishawack Archimed
includes a mix of physicians, PhDs,
pharmacists and pharmacologists, as
well as employees with long-standing
drug development experience in
the industry.
The Fishawack Group is one of
the largest independent medical
communications specialists,
with offices in the UK, the US,
and Switzerland.
For more information please contact:
Violetta Kyburz
Commercial Director
Fishawack Archimed
Dr Charlotte Maddox
Director of Pharmacovigilance Services
Fishawack Archimed
t +41 79 698 83 71
e [email protected]
t +41 62 746 83 29
e [email protected]
www.fishawack-archimed.com
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