Beruflich Dokumente
Kultur Dokumente
Amsterdam
15-16 February 2016
Conference report
AESGP Conference with EU Heads of
Medicines Agencies (HMA) during
the Dutch EU Council Presidency
Session 1
From LEFT to RIGHT: Hubertus CRANZ, Andrzej RYS, Kristin RAUDSEPP, Hugo HURTS, Andr BROEKMANS
Session 2
Christa WIRTHUMER-HOCHE, Acting Chair of the EMA Management Board and Head of the Austrian Medicines and Medical Devices Agency, set the scene of the second session by recalling the challenges and opportunities of the 21st century: an increasingly aging population, more long-term and chronic conditions, a changing landscape in the pharmaceutical industry, a changing healthcare landscape with empowered patients and
self-care playing a key role in the European economy, and lastly globalisation of manufacture and supply
chains. She wondered whether the +1 year of data exclusivity in case of significant preclinical test or
clinical data in case of switch (vs. 3 years in the US and Japan) was enough to promote innovation. In
her view, an innovative self-care is part of the answer to the current challenges in healthcare and it
should be adequately encouraged and rewarded.
Conference report
anefp, developed a list of indications and applicable models of product information leaflets
(PILs). This work revealed that having a common
Summary of Product Characteristics (SmPC) for
products with the same active substance, dose,
indication, etc., but two different PILs depending
on the condition of prescription-only or nonprescription medicines would be helpful. In addition, package sizes and doses need to be aligned
with the indication. She concluded on the fact that
self-care is today key to healthcare. Medicines
Agencies will be increasingly confronted with a
changing society in which citizens are more and
more empowered to make their own decision and
demand more self-care choices.
John BORG, CHMP and EMA Management Board member from Malta,
echoed the view of the previous speakers that due to the societal
changes, more non-prescription medicines with new indications will be
needed in the future to fulfil expectations from empowered patients. He
referred to the PiSCE project in self-care in the EU as an example of political drive to build the right environment. Regulatory-wise, benefit-risk
models would be useful guides to decision-making. He particularly
referred to the Brass model on benefit-risk evaluation for nonprescription medicines as a very interesting model. As closing remarks, he gave a number of possible solutions to centralised switching:
To Christelle ANQUEZ-TRAXLER, AESGP Regulatory and Scientific Affairs Manager, the availability
of non-prescription medicines in Europe needs to
be addressed (currently only 7 APIs are available
without prescription in all 28 Member States)
and for this reason AESGP was pleased to see
that improving patient access to [....] nonprescription medicines was a concrete objective
of the EU Medicines Agencies Network Strategy
to 2020. She reminded participants of the Tajani
report on the promotion of good governance of
non-prescription medicines which emphasised
the use of non-prescription medicines not only
for minor ailments but also for chronic disease
management and disease prevention in the
frame of the collaborative care concept between
patients, pharmacists and doctors. Looking outside Europe, oxybutynin was made available without
prescription in the US, and New Zealand was the
first country in the world to change the legal status
of sildenafil, calcipotriol and oseltamivir to nonprescription. What about Europe? In Europe, four
medicines were switched using the centralised
procedure (orlistat, pantoprazole, esomeprazole
and ulipristal). To unblock the procedure and provide the possibility to generate data concerning the
availability of a medicine in a self-care environment,
AESGP had developed a proposal including:
Early stakeholder dialogue between the applicant, patients, CHMP members, and healthcare
professionals.
Use of the Brass model on benefit-risk for nonprescription medicines and
Marketing authorisation issued either without a
Post-Authorisation Safety Study (PASS --ideal
scenario) or with a PASS and launch at national
level in 2 phases: first in countries agreeable to
have the product switched and welcome the
PASS study on their territory and then a couple
of years later in the second group of countries
once the PASS data have been generated.
Bernard MAURITZ, Director of Neprofarm, explained that half of the counterfeit medicines are sold over the internet from dubious websites (i.e. illicit channels) and he doubted that the obligatory logo alone would change this. He
explained the various reasons why non-prescription medicines are
exempted from serialisation e.g. that counterfeiters are not interested in
counterfeiting non-prescription medicines given the fact that they are
inexpensive. The only exemption is for products responding to the criteria set
in the legislation and being listed (blacklist). The voluntary application of
safety features on other non-prescription medicines is not allowed. Member
States may require anti-tampering device on all medicinal products, including
non-prescription and safety features on all reimbursed medicinal products.
Conference report
The topic of the electronic leaflet was also addressed. Andrzej RYS mentioned the study on product information realised by NIVEL which will be followed by the Commissions report (called by the legislation).
For AESGP, the package information through labelling and / or package leaflets remains a requirement as
there often is no interaction with healthcare professionals and non-prescription medicines may be used by
the whole family and not only directly after purchase. The package information may however be complemented by electronically-available product information.
Session 3
From LEFT to RIGHT: Peter BACHMANN, June RAINE, Elmar KROTH, Xavier DE CUYPER, Paul CARTER, Peter ARLETT
Specific to non-prescription medicines and crucial to the success of a switch is the use of scientific
advice, now permitted by the formalised link between the Pharmacovigilance Risk Assessment Committee
(PRAC) and the Scientific Advice Working Party (SAWP) with a common member.
The last item of his speech concerned the Medical Literature Monitoring system provided by the Agency
which will look at service improvements based on industry feedback.
Elmar KROTH, Director of the German Medicines
Manufacturers Association (BAH) and member of
the AESGP Pharmacovigilance Committee, echoed
some of the successes of the pharmacovigilance
legislation, notably in terms of simplification with
a reference to the Article 57 database use for the
purpose of notifying changes to QPPV details.
However, there is a clear plea for a more riskbased approach which should take into consideration the fact that the vast majority of nonprescription medicines are nationally authorised products, meaning that all procedures need
to be consequently adopted at national level.
A strategy should be identified to make the Medical Literature Monitoring system more beneficial, in
particular through a simplified data exchange between the Agency and companies and a more harmonised approach between European and other world regions. Solutions could possibly be found during the monthly pharmacovigilance cluster between the European Medicines Agency, the United States
Food and Drug Administration (US FDA) and Health Canada, with the participation of Japans Pharmaceuticals and Medical Devices Agency (PMDA) as an observer.
The industry experience on referral procedures
was provided by Paul CARTER, Global Head
Consumer Health Care, Development, Medicine
and Regulatory Affairs within Boehringer Ingelheim, a company concerned by an almost twoyear long procedure. The different formulations
and indications, correlated with specific different profiles in terms of safety, have added to
the complexity of the ambroxol/bromhexine
referral. Ambroxol and bromhexine have been on
the market respectively for more than 30 and 50
years with an exceedingly well-established use
lined with millions of patient-years in terms of
safety data. Being the originator of both substances, Boehringer Ingelheim had also built an extensive database for ambroxol and bromhexine. The
referral started at the end of the PSUR work-sharing procedure in Europe. Two points were at the heart of
the referral procedure: an increase in the rate of reporting of hypersensitivity, which was found to be an
artefact from the Chinese use of the product in the post-operative pulmonary complications (PPC) indication, and Severe Cutaneous Adverse Reactions (SCARs) with a question as to whether this is a temporal or a
causal factor of the use of ambroxol/bromhexine-containing medicines. The moving target from safety to
efficacy questions was a serious threat in the procedure, with some views within the PRAC that the benefit/risk of these medicines was negative.
Conference report
The 8-week period to provide responses to the PRACs list of questions thereby not allowing alignment with
industry partners and the difficulty to provide data on the clinical use, which is hard for well-established
substance, were also challenges. Real-world data (how do physicians/consumers/pharmacist value and use
our products?) provided by the company was ignored by the PRAC. There has to be a different way of
assessing well-established products by taking consumers views into consideration said Paul Carter.
Dialogue and communication along the process should also be facilitated.
June RAINE, Chair of the European Medicines
Agencys Pharmacovigilance Risk Assessment Committee, recognised that referrals need to be used
wisely and carefully; in practice, the number of
referral procedures went from 18 in 2013 to 5 in
2015 with no urgent review since July 2014. Thanks
to a collective work of everyone engaged in these
important new procedures, effective signal detection, effective PSURs and proactive risk management plans, we are in Europe for the very first time
over new risk. said Dr Raine. The possibility of
setting a different timetable in line with the
data, responses and emergency of the matter
has to be reflected, especially for wellestablished substances.
An update was also provided on the two ongoing surveys: feedback is expected in Q3 2016 on the codeine
study which uses the IMS data from France, UK and Spain, while the qualitative and quantitative studies on
combined hormonal contraceptives are still ongoing.
Last to speak was Peter BACHMANN, Chair of the
Co-ordination Mutual Recognition and Decentralised procedures-human (CMDh), who provided
further insight on the referral on fusafunginecontaining medicines initiated in September 2015.
The rationale behind this decision was linked to an
Article 107 (1a) Urgent Union procedure which
means that, for medicinal products authorised
through a mutual recognition procedure or a decentralised procedure, the case shall be brought to
the attention of the CMDh in cases where a referral
was not initiated.
According to Peter Bachmann, in case of safety issues for purely nationally authorised products, companies should consider work-sharing variation applications for updating the product information of these
products with regard to safety information and avoid duplication of assessment. According to Mr Bachmann, this is what went wrong for fusafungine-containing medicines, as the marketing authorisation holder
chose to submit purely national variations at different points in time in different Member States in order to
update the SmPC. Consequently, the non-harmonisation in the SmPC updated wordings was informally discussed within the CMDh in March 2015, with a proposal for a common harmonised wording further discussed
in April. Member States felt the need to reassess the contraindications of fusafungine-containing medicines in
children without having the possibility of properly reviewing this concern within the scheme of any procedure.
In May 2015, the CMDh concluded that a change of PSUR would be requested; however, considering that the
outcome of an assessment of a PSUSA would only be available in several months, it was concluded that a
referral procedure could be pursued, which was done four months later at the request of Italy.
In general, all speakers agreed and converged on the need to place real-world evidence in the centre of
scientific discussions in the future, which AESGP hopes to see duly applied.
Session 4
early with regulators to plan a switch and discuss the evidence that can/should be generated.
It is important to reconcile real-world evidence,
enable patients and plan a switch at the beginning of the lifecycle of a medicine so that the
knowledge can be generated in time. Real-world
data (RWD) can be used to get evidence and check
the initial hypothesis. Many RWD initiatives are
ongoing in Europe at the moment. There is the
opportunity to use new technology and realworld evidence to empower patients. Connected
to this, he announced that the EMA will hold a
workshop on big data in the near future to get
guidance on how to use them and not be misled.
Guido RASI ended his presentation by wondering
whether now is the time for switch by design.
Jonathan MOGFORD from the MHRA gave Ian Hudsons presentation given that the latter had to cancel his participation at
very short notice due to illness. He referred to the EU Medicines
Agencies Network Strategy to 2020 which will be supported by
separate individual multi-annual work plans (MAWP). The HMA
MAWP, which is aligned with the EMA MAWP, contains 11 overarching priorities which are declined into 63 individual actions.
Amongst the 11 priorities are: antimicrobial resistance, availability
of appropriately authorised medicines, innovation and access to
new medicines, support for better use of medicines. He gave a
glimpse of individual actions contained in the draft MAWP:
Jonathan MOGFORD
Conference report
HMA will continuously explore the harmonisation of criteria and the removal of unnecessary
national requirements to reduce the administrative burden of registration processes in
Member States
HMA will explore other ways to reach agreements between Member states regarding nonprescription products, to facilitate a greater
number of product switches
Optimisation of the regulatory framework,
including continuing to collaborate to reduce
regulatory burden where appropriate, having
captured the needs and expectations of stakeholders
Proactive engagement with stakeholders on
key strategy areas and agreeing joint plans of
action
Develop more streamlined mechanisms to
obtain regular feedback from key stakeholders
on the operation of HMA activities and the
quality of the output
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Conference report
At the end, conference participants were invited by the AESGP President to the AESGP Annual meeting taking
place in Athens from 31 May to 2 June.
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