Conference report

Opening Evening in the European Parliament

The meeting started with a well-attended evening event
in the European Parliament hosted by Adina-Ioana
Vlean, Chair of the Committee on the Environment,
Public Health and Food Safety (European Parliament),
who cordially welcomed participants and underlined the
importance of the self-care industry for offering product
choices and for providing the necessary information.
AESGP also had the honour of the presence of Commis-
sioner Vytenis Andriukaitis who, in his speech, shared
his thoughts on the role of self-care in managing the
increasing pressure on health systems. A greater focus
on prevention and prophylaxis in addition to early di-
agnostics and treatment are essential stressed Mr An-
driukaitis, self-care and empowerment can make pa-
tients more autonomous and by extension less depend-
ent on our health systems.

At the AESGP event in the European Parliament on 10 October 2017 (from left to right): Hubertus Cranz (AESGP Director General),
Adina-Ioana Vlean (European Parliament), Vytenis Andriukaitis (European Commission), Renate Sommer (European Parliament),
and Dirk Ossenberg-Engels (AESGP Vice-President, Bayer Consumer Care)

1
Two projects relating to self-care have been funded by
the European Commission: PiSCE, a project of self-care
systems in the EU, and PRO STEP, which promotes self-
care in chronic diseases. The PiSCE project developed
guidelines and communication tools on how to pro-
mote self-care for chronic diseases. This can contribute
to improved patient centred care. The Commissioner
furthermore stated : The project also provides recom-
mendations for the implementation of non-prescription
drugs and stresses the importance of early involvement
of stakeholders, training of health professionals and
improving the knowledge and skills of citizens and pa-
tients. He underlined the investment in self-care as an
integral part of health literacy in education system.
The Commissioner explained the patients need for
tools to strengthen their knowledge and better monitor
their condition. This includes a wide range of medical
devices and mHealth tools, some of them used in a self-
care context, whose safety and effectiveness will be
ensured by the two new Regulations.
Mr Andriukaitis also focused on anti-microbial re-
Food Products and Health
Session 1
Which Direction to Go?
The Health Claims Regulation - A Mistake
from the Very Beginning?
Dr Renate Sommer introduced the session with an an-
ecdote about how difficult it was for her daughter to
find regular milk in the United States. Almost all types
of milk were labelled as fortified or lactose free. She is
glad that we do not yet live in such conditions because
EU requirements for making such claims are very high.
However, she remarked that the US legal setting might
be preferable for some manufacturers. The market for
foodstuffs is saturated and it makes sense to add to
food to make it functional to place new products on the
market. She pointed to the success of functional foods
and the willingness of consumers to pay a higher price
for them in the supermarket. She noted that lots of pro-
ducers of functional foods and food supplements are
Small and Medium-sized Enterprises (SMEs), who con-
stitute the draft force of economic growth in the EU.
sistance (AMR), one of the major priorities for the Com-
mission which adopted the EU One Health Action Plan
against AMR. He outlined that in July the Commission
published guidelines on the prudent use of antimicrobi-
als in human medicine, which stress the importance of
avoiding treatment when there is only evidence of a
viral infection such as the flu or of an infection after rel-
evant clinical examination. Non-prescription medicines
can play an important role in alleviating the symptoms
of patients who do not require antibiotics to treat minor
ailments and disorders.
At the end of his speech, he stressed the collective re-
sponsibility in the development of healthy societies and
sustainable health systems, encouraged an open and
insightful debate including all stakeholders and wished
the participants a fruitful conference.
AESGP Director General, Hubertus Cranz, thanked both
Mrs Vlean and Commissioner Andriukaitis for their im-
portant statements and underlined the commitment of
the European self-care industry to address healthcare
challenges such as antimicrobial resistance.
The EU and its institutions did therefore not want to
prevent such innovation, although the Commission did
attempt to regulate the use of food supplements and
medical components in foodstuffs. She remarked that
from her perspective the scientific evaluation with re-
gard to the amounts of vitamins and minerals that may
be added to foodstuffs in the EU was quite successful.
She believes that Regulation (EC) No 1925/2006 on the
addition of vitamins and minerals and of certain other
substances to foods ensures that food supplements are
added in a manner that ensures a positive effect on
health while preventing an oversupply of certain sub-
stances. However, regarding advertising of these inno-
vative foods, she believes the EU has failed.
Large parts of the Nutrition and Health Claims regula-
tion, Regulation (EC) No 1924/2006, that was intended
to regulate advertising claims, are not in force yet. The
evaluation of the vast majority of claims submitted for
approval took years and 80% of evaluated claims were
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denied. She added that this was also a heavy burden for tions in the Parliament show that MEPs are sceptical
EFSA. That was when the EU postponed the evaluation towards new claims, and rejected several claims such as
of botanicals claims. Up until now, there has been no the effect of caffeine or carbohydrates. Mrs Sommer
new progress on 1600 claims on botanicals leading to concluded that from her perspective ideally all health
market distortion and legal uncertainty for all stake- claims should be banned.
holders. Manufacturers whose claims have already been
denied are particularly disadvantaged as other botanical Pharmafoods and Botanical Claims State
claims are still unregulated and allowed. Equally the of Play
Commission has not yet come up with a proposal for
the nutrient profiles, which should have been the basis
Nathalie Chaze, Deputy Head of Cabinet of Commis-
for the entire regulation. The Health Claims Regulation
sioner Vytenis Andriukaitis, European Commission, ex-
judges on single foods, but it is nonsense to think that
plained that the overall food policy in the EU is under
people eat just one food all the time. She therefore
review, as a number of re-evaluations and REFIT
believes that the Health Claims Regulation was a
(Regulatory Fitness and Performance Programme) exer-
mistake from the very beginning, as to date, 9 years
cises have been launched to assess whether it is fit for
after it came into force, the most important elements
purpose and aspects of the legislation have not been
are still missing.
implemented. This is being carried out not just for the
Health Claims legislation but also the General Food Law
Meanwhile, the Regulation on the provision of
which is celebrating its 15-year anniversary this year
food information to consumers (FIC) (Regulation (EU)
(end of November). We have a good system in place to
No 1169/2011) is implemented, which in her view
ensure food safety, which was why the General Food
makes the health claims regulation superfluous. She
Law was established in the first place, and its not easy
believes that if we want to educate people on how food
and we face regular crises and it is never a finished job,
can contribute to health, we should inform consumers
it is ongoing, she explained. The REFIT exercise also
on a balanced diet and the composition and prepara-
looks at the re-evaluation of the pesticide legislation.
tion of food. This does not mean that the inclusion of
vitamins and minerals should be prohibited, however, if
She acknowledged the challenges faced, particularly in
consumers are better informed, they can use the FIC
recent years, in relation to science, as scientific opinions
Regulation to decide for themselves. Food labelling al-
with an unfavourable outcome were challenged. It is
lows consumers to see immediately if the product is
difficult to take a decision as policy makers, as civil soci-
supplemented with vitamins and minerals as it has to be
ety and stakeholders challenge scientific opinions. In the
included in the ingredients list, and can be added to the
field of food, it is one of the first challenges we are fac-
nutrition declaration, which can act as a marketing in-
ing and we see it in different fields. Another challenge,
strument. Article 7 of the FIC Regulation further protects
she explained, is the evolution in consumer choice.
consumers from misleading information.

In the past, food safety and quality were the main con-
cern. Now, more and more, food is seen as a means for
physical health and no longer just for nutrition. She al-
luded to the Joint Research Centres (JRC) study pub-
lished by the Commission which looks at EU Health and
Nutrition in 2050. The study describes different scenari-
os of where food will go, and one of them is
Pharmafoods. We are seeing this trend more and
more in society, in particular with the growing trends in
obesity, food needs to be healthy and maximise our
healthy life years. There is a huge demand from society
for truth about healthy food. This is why, she explained,
Nathalie Chaze the Health Claims Regulation plays an important role.

It was established to ensure that customers would have

The European Parliament asked to review the Health
information about food which was not misleading and
Claims Regulation in the REFIT procedure. Recent objec-
that health claims were approved after scientific assess-

3
ment by EFSA. The level of scientific evidence required
to make such claims, however, is quite high. Applying
the same scientific evidence requirement for food and
botanicals was therefore extremely challenging for the
Commission as it has a significant impact on the prod-
uct and on the market. In addition, would the EU society
be ready to accept that the Commission rejects all
health claims on botanicals?
The lines are blurred between what constitutes a medi-
cine and what constitutes a food. She believes the Com-
mission has been lenient when it comes to health
claims. Although they have rejected a lot, they have
permitted quite a few. Regarding botanical claims, the
Commission is looking for a solution and is aware of the
issue.
She believes that the intention of the Health Claims
Regulation is to provide consumers with accurate infor-
mation. By banning all claims, she believes, an infor-
mation vacuum might be created which needs to be
addressed. The Health Claims Regulation does not ad-
dress requirements for production, quality and safety
for botanicals to the same extent as their evaluation as a
medicine, and she believes that we should maybe have
looked beyond health claims for botanicals and that we
stopped short in 2006 when attempts were made to
regulate botanicals.
The Commission is looking in particular at the playing
field between botanicals and herbal medicines, which
sometimes contain the same ingredient, or may be clas-
sified in one Member State as a botanical and in anoth-
er as an herbal medicine. These different regulatory
frameworks can create distortions in terms of the EU
single market.
An important question we are faced with is whether we
can have different regulatory frameworks if it cannot be
clearly defined at EU level, as the purpose of the legisla-
tion is not to give a competitive advantage to a catego-
ry of food supplement over another. We need to have a
consistent and balanced approach.
Regarding the timelines for the REFIT evaluation, the
Commission is waiting for the contractor to prepare its
report by the end of 2017. The draft final report of the
study will be presented to stakeholders at an ad hoc
working group meeting on nutrition and health claims
on Friday, 27 October 2017. Results of the evaluation
are expected for the second quarter of 2018.
As society becomes more health conscious, and the
trend towards self-care increases, she remarked that the
question of which direction we are going with regard to
food is very timely.
The Assessment of Other Substances
Added to Food by EFSA
Camilla Smeraldi, Senior Scientific Officer, in the Food
Ingredients and Packaging Unit of European Food Safe-
ty Authority (EFSA), presented EFSAs role in the safety
assessment of certain other substances added to foods.
Annexes I and II of the so-called Fortification Regula-
tion (Regulation (EC) No 1925/2006 on the addition of
vitamins and minerals and of certain other substances
to foods) list vitamins and minerals and their formula-
tions which may be added to foods. Annex III, which
applies to foods in general and food supplements, lists
certain other substances whose use in foods is prohibit-
ed, restricted or under Community scrutiny. Article 8 of
this Regulation forms the legal basis for a safety assess-
ment of certain other substances by EFSA.
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Article 8 procedure

After a safety assessment by EFSA, the Commission, on
the basis of the EFSA opinion, will take a decision to
restrict the substance by placing it in Part A (prohibited)
or Part B (restricted) of Annex III if a harmful effect on
health is identified, or in Part C (under Community scru-
tiny), if scientific uncertainty persists on the identifica-
tion of potential harmful effects on health.
She explained that to start an assessment EFSA needs a
mandate. In the case of Article 8, procedures carried out
by EFSA always come from the Commission, either of its
own initiative or on request from the Member States. In
the latter case, the request must contain available and
relevant generally accepted scientific evidence that the
substance is added to food, the amount exceeds what
could be expected in the diet and evidence on its po-
tential risk to the general population.
Article 8 procedure. The ANS panel supports the deci-
sion-making procedure in the authorisation procedure
for new food additives/changes to permitted uses and
the re-evaluation of permitted additives since 2009. The
ANS panel in EFSA also has self-tasked mandates and is
due to publish an opinion on the approach followed for
the refined exposure assessment as part of the safety
assessment of food additives under re-evaluation. The
panel is also in the process of drafting Guidance on the
Evaluation of Nutrient Sources. With the evaluation of
nutrient sources there is an overlap with the NDA panel
as often it is involved in novel food assessment.

To start a scientific assessment EFSA always needs a

mandate which contains the question the scientific
opinion needs to answer. Ten scientific panels support
the remit of EFSA. These are composed of independent
experts who evaluate the data (available data is re-
trieved from the literature and calls for data are
launched), provide the scientific assessment and pre-
pare the draft opinion in multidisciplinary working
Camilla Smeraldi
groups.

She then described the current structure of EFSA. The
NDA (Panel on Dietetic Products, Nutrition and Aller-
gies) panel is tasked with the evaluation of health
claims. The Assessment of Nutrient Sources (ANS) panel
is currently tasked with the safety assessment of food
additives, nutrient sources and the bioavailability of the
nutrient from the sources, and safety assessments under
However, as of July 2018, all EFSAs scientific panels will
be renewed. The ANS panel will be re-established as the
panel on Food Additives and Flavourings (FAF), tasked
with the safety assessment of food additives and fla-
vourings. The new panel will hand over responsibility for
the evaluation of nutrient sources and the evaluation of
Article 8 procedures to the NDA panel, which makes

5
sense as often Article 8 procedures are a direct follow-
up of a health claim evaluation.
EFSA has a limited experience with safety assessments
conducted under this regulatory framework. In total, five
mandates have been received to date, all related to sub-
stances from botanical sources, mainly used as food
supplements ingredients.
In August 2012, EFSA received two mandates from the
Commission regarding Yohimbe and Ephedra species
triggered by the Member States, in particular, BfARM,
the Federal Institute for Drugs and Medical Devices in
Germany. As a result of the EFSA scientific assessment,
Yohimbe was placed under Community scrutiny (part C
of Annex III) in 2015 and Ephedra was placed in the list
of substances which are prohibited (part A of Annex III).
In the case of Yohimbe, a valid dossier was not received
so the Commission must take a decision to restrict, pro-
hibit or allow Yohimbe by April 2019.
For substances placed under scrutiny in Annex III Part C
(i.e. harmful effects are identified but scientific uncer-
tainty persists) a follow-up mechanism is foreseen by
the legislation. There is a period of 18 months for food
business operators to submit a follow-up opinion dossi-
er to EFSA. The evaluation by EFSA has to be completed
9 months from the date of receipt of a valid dossier. So
far, there has been no experience with the follow-up, if
the dossier can come from groups of interested parties
for example, or if it can be product specific. Within 4
years from the date a substance has been listed in An-
nex III, Part C (under Community scrutiny), the Commis-
sion must take a decision to either generally allow the
use of the substance or list it in Annex III, Part A
(prohibited) or B (restricted) as appropriate. This deci-
sion should take into account any further opinion of
EFSA based on dossiers submitted by any food business
operators/interested parties.
EFSA currently has three ongoing mandates. One of
these, relating to Hydroxyanthracene derivatives, was
started by the Commission of its own initiative and is a
follow-up of an earlier health claim opinion issued by
the NDA panel on the substantiation of a health claim
related to an improvement of bowel function. Five pos-
sible botanical sources have been identified: Aloe, Rhu-
barb, Cascara, Senna and Frangula. The assessment is
ongoing with preliminary conclusions presented to the
ANS Panel in September 2017. An extension of the
deadline was requested from the Commission to allow
for a call for data. The opinion is to be adopted by the
end of November 2017.
The Commission initiated another Article 8 procedure
shortly afterwards, on request from Member States
(Denmark, Sweden and Norway) following safety con-
cerns related to hepatotoxicity with Green tea catechins,
in particular (-)-Epigallocatechin-3-gallate (EGCG). The
assessment is ongoing and a draft opinion was dis-
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cussed by the ANS Panel ad-hoc working group in Sep- monisation among Member States can make enforce-
tember 2017. An extension of the deadline until Q1 ment by the Commission in the area of food supple-
2018 was requested, as the US pharmacopeia is con- ments difficult. In the case of classification, it could take
ducting a similar assessment. years to get the food off the market.

The last mandate received relates to Monacolins in red
yeast rice. The procedure was initiated by the Commis-
sion of its own initiative and is a follow-up of a health
claim issued related to monacolin K from red yeast rice
and the maintenance of normal blood LDL-cholesterol
concentrations. The assessment is ongoing, and a public
call for data was just launched. Completion of the as-
sessment is anticipated for February 2018.
She pointed out that although vitamins and minerals
are harmonised, the maximum amounts are not, which
causes a lot of issues. There is also no harmonisation of
botanicals and other substances, which makes it difficult
to enforce. She is also a strong supporter of the Health
Claims Regulation, as the presentation of a product af-
fects whether it is seen as a medicine or not.

Food Supplements and Internet Sales

A View from Austria

Dr Amire Mahmood from the Federal Ministry of

Health, Austria, began by recalling a previous AESGP
conference on the then newly released Food Supple-
ments Directive 2002/46/EC, where she believed maxi-
mum levels of vitamins and minerals would be estab-
lished by 2006. Now in 2017, it is still not harmonised.

As a Member State she supports harmonisation in the

area of food supplements and health claims, which she
Amire Mahmood
can especially appreciate working in the Federal Minis-
try of Health in Austria and hearing the issues in the
As more and more claims are found on the internet ra-
food industry. The main problem with food supple-
ther than on the product, it is not easy for competent
ments, she explained, is classification. The lack of har-

7
authorities to find these claims. The new Official Con-
trols Regulation (Regulation (EC) No 2017/625 on offi-
cial controls and other official activities performed to
ensure the application of food and feed law rules on
animal health and welfare, plant health and plant pro-
tection products, which replaces the old Regulation (EC)
No 2004/882) hands over more power to food authori-
ties and will come into force by the end of 2019.
It allows food inspectors from the ministry to perform
mystery shopping. Samples can be ordered from food
business operators by the competent authorities with-
out identifying themselves for the purposes of an offi-
cial control. The food business operator needs to be
informed that such samples have been taken, and must
have the right to a second expert opinion. In the case of
non-compliance there is a possibility for food inspectors
to cease the internet activities of the food business op-
erator for an appropriate period of time.
The European Commission recommendation on a coor-
dinated control plan on internet sales, which came out
in July 2017, asked Member States to look more at bone
and joint health supplements with medicinal claims and
four novel foods are listed as non-authorised: Agmatine
(4-aminobutyl) guanidine sulfate, Acacia rigidula,
Epimedium grandiflorum and Hoodia gordonii. The aim
was to strengthen the cooperation and administrative
assistance between Member States and practise using
RASFF (the Rapid Alert System for Food and Feed) and
AAC (AA) and AAC (FF) for a fast exchange. The AAC
(Administrative and Assistance Cooperation system) is
an IT system set up for EU countries to exchange data in
a structured manner regarding non-compliance with
food and feed legislation. Since August 2016, the sys-
tem has been split in two parts: a part dedicated
to Food Fraud and the Food Fraud Network, and a part
dedicated to every request for Administrative Assistance
and Cooperation which does not present health risks.
The intention was also to signal to food business opera-
tors that e-commerce control is taken seriously by the
competent authorities and to build experience and ca-
pacity with the enforcement of food law towards inter-
net sales of food.
Each Member State looked at websites which offer
food in their official language. So far no mystery shop-
ping was required. There was a control period and now
the notification period is ongoing. Notifications were
made via RASFF or via AAC (AA). Dr Mahmood hopes
that this co-operation works and finds products which
should be removed from the market so that food busi-
ness operators can be adequately controlled.
Regulatory Gaps and Legal Uncertainty
Speaking from the consumer perspective, Ilaria Passa-
rani, Head of the food and health department, Europe-
an Consumer Organisation (BEUC), opened the discus-
sion with a metaphor of EU society at a crossroads for
many food policies issues. This hesitation, she ex-
plained, is at the expense of consumers rights to infor-
mation and consumer health and she is looking forward
to some action. She explained that while we wait for
decision makers to show us the way forward, consumers
remain confused over similar products and are exposed
to misleading claims and health risks.
Ilaria Passarani
She then described how consumers may feel confused
with the example of a botanical regulated as an herbal
medicinal product and a food supplement. St. Johns
Wort (Hypericium Perfortum), which is sold in Spain as a
8

herbal medicine and in Belgium as a food supplement.
Both products make slightly different claims. For the
herbal medicine it is the systematic treatment of fatigue
and loss of interest, and for the food supplement claim
it is a balancing effect on mood swings. The herbal
medicine warns against several interactions and side
effects while the food supplement does not. This dispar-
ity, she warned, can have an important impact on pa-
tient safety. Even if botanicals only make minor claims,
it is vital to guarantee that these claims are justified and
that these products live up to the promises they make.
She therefore believes botanical claims should be evalu-
ated by EFSA as all other claims, and should not be
granted special treatment.
Regarding the ongoing revision of the Health Claims
Regulation, the Consumer Association believes that, to
protect consumers from exaggerated and unsubstanti-
ated claims, if there is no evidence, there should be no
claim. However, if botanical claims are questioned, she
fears that all claims rejected by EFSA under Article 13
might be challenged, which the Consumer Association
do not want.
Commenting on the REFIT evaluation of the Health
Claims Regulation, she said we are evaluating some-
thing that hasnt been implemented and hasnt yet pro-
duced an impact. She believes this is a dangerous path
to take as it could extend to other legislation.
Another pending issue she reflected on is the lack of EU
harmonised maximum levels for vitamins and minerals.
The Stiftung Warentest test in Germany showed the risk
of too high doses of vitamins in food supplements (5
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Conference report
times greater than the levels recommended by BfARM).
The Consumentenbond test used in the Netherlands
found that 3 of the 5 food supplements examined con-
tain much more or much less iodine than the label indi-
cates. Some of these products were withdrawn while
others remain on the market. Establishing maximum
and minimum limits as well as deviation margins for
vitamins and minerals is long overdue, so that consum-
ers are not exposed to either too low doses or too high
doses, she explained.
She believes that more controls are needed for food
supplements sold online to protect consumers from
dangerous products, as information on interactions and
side effects is often not available. The Commission rec-
ommendation on official controls for products sold over
the internet is a welcomed step, as RAPID safety alerts
for food supplements have more than doubled since
2010.
As a consumer association, she hopes that decision-
makers will find the right direction and be guided by
key principles, putting consumers safety at the centre:
products should be safe, especially those used for
health, consumers should get value for money and
products should be effective, classification should be
coherent and based on the characteristics of the prod-
ucts and rather than the possibility to make health
claims, consumers should be informed and all claims
should be substantiated by good evidence. This applies
to all consumer products. If the EU wants to reconnect
with its citizens it needs to act quickly, she said. If we
dont act quickly, we risk losing consumer confidence in
these products, and this is no ones interest.
 The Real Implications of The New Medical
Session 2
Device Legislation
Moderated by Gesine Meissner, Member, Committee
on Environment, Public Health and Food Safety (ENVI),
European Parliament, and shadow rapporteur for the
political group of the liberals during the legislative pro-
cess for the Medical Devices Regulation (so-called
MDR), this session looked at the implications of the
new medical device legislation. Mrs. Meissner remarked
that the legislative process was difficult and alluded to
the challenges ahead with the implementation of the
legislation.
Gesine Meissner
Novelties of The New Medical Devices Reg-
ulation - The Commissions Perspective
Carlo Pettinelli, Director, Consumer, Environmental and
Health Technologies, Directorate General Internal Mar-
ket, Industry, Entrepreneurship and SMEs, European
Commission, opened the session by acknowledging the
crucial role of medical devices in self-care and as such
the sustainability of health systems. He thanked for the
commitment of all stakeholders that as of May 2017,
after 5 challenging years, the EU legislation for Medical
Devices has become law, and the EU now stands at the
forefront of innovation and progress in this field in the
world.
He firmly believes that the legislator has managed to
stick to the principles of balance and proportionality
and while the regulation will allow a uniform application
of its rules, the system will undergo a deep evolution
rather than a revolution. It will build on characteristics
of the older system, for example, the central role of no-
tified bodies in the certification process and the balance
between post and pre-market controls, while address-
ing the scandals arising in recent years, adapting the
rules to technological advances, and thereby increasing
patient confidence in the system.
Novelties introduced by the legislation include the pre-
market control for manufacturers of high risk devices
with the involvement of a pool of experts at EU level.
Another is the enforcement of the criteria for the desig-
nation and oversight of notified bodies. In particular the
new regulation reinforces the joint assessment of noti-
fied bodies, already introduced in 2013, a system
through which experts from Member States and the EU
Commission, jointly assess the competence and perfor-
mance of notified bodies. The medical device regulation
now also covers devices not used for a medical purpose,
which present the same characteristics and have an
analogous profile to an existing medical device, for ex-
ample, contact lenses used for aesthetic purposes. It
will increase transparency through the establishment of
a comprehensive database of the lifecycle of all medical
devices available on the EU market, which will be largely
publicly available. The regulation will also introduce a
stricter regime related to the use of hazardous sub-
stances and requirements for an implant card to be giv-
en to patients containing information about the im-
plant. It will reinforce the rules on clinical evaluations
and investigations, including an EU wide co-ordinated
procedure for clinical investigations taking place in
more than one Member State. It will also improve co-
ordination between Member State in the fields of vigi-
lance and surveillance. Obligations of economic opera-
tors have been specified and detailed and the roles and
responsibilities of authorised representatives are being
reinforced.
In respect of substance based medical devices, he ex-
plained that they will be subject to a new classification
Rule 21. Rule 21 was introduced to fill a legislative gap.
The old legislation on medical devices adopted 20 years
ago was not conceived with these products in mind.
Consequently, they generally fell in class I without a
consideration of their risk. This was later unanimously
10

seen as problematic, as some of these products are of-
ten used by vulnerable patient groups and are available
without prescription. The new legislation ensures that
the safety of these products is appropriately checked by
notified bodies. However, the strictest conformity as-
sessment procedure is only reserved for those products
which are systemically absorbed. He believes that, in
respect of substance-based devices, they succeeded in
negotiating a proportionate and risk-based approach.
Carlo Pettinelli
In the context of the qualification and classification of
borderlines, there will be more legroom to take the
Commissions decision on the regulatory status of prod-
ucts, as the Commission will now be able to initiate a
decision procedure of its own initiative.
In co-operation with the future Medical Device Co-
ordination group (MDCG), the Commission intends to
take initiative whenever needed to ensure that the inter-
nal market functions in an efficient manner and that
patients rights are guaranteed. At the same time, stake-
holders are always in a position to input their views and
opinions.
The effective and timely implementation of the legisla-
tion is crucial to ensure that expectations are properly
fulfilled and is a challenge which lies ahead. The Com-
mission is keen to ensure that the new system brings
added value for all stakeholders.
Anticipating questions AESGP has on whether the Com-
mission has enough resources to make all this happen
and to what extent stakeholders will be in a position to
inform the implementation process, he explained that
the Commission intends to allocate sufficient staff to
this task. The Commission services have already started
work on the secondary legislation, relevant guidance
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Conference report
and the Eudamed database since last year. On the sec-
ond question, he highlighted that not only does the
Better Regulation framework give stakeholders an in-
creased opportunity to comment, the new legislation
assigns a key role to stakeholders in expert groups.
Commission communication with stakeholders has al-
ready taken place. The Commission and the Competent
Authority for Medical Devices (CAMD) organised on the
9th March 2016 the first stakeholder workshop with an
exchange of views on the workplan for the coming
years. The next workshop on 18 October 2017 will final-
ise the roadmap for the new medical device regulation.
The roadmap will set the timing and framework of fu-
ture deliverables for the Commission and Competent
Authorities mainly interpretative and operational guid-
ance for the medical devices regulation.
In light of this, he is confident that the real implications
offer concrete opportunities for EU medical devices pa-
tients and the health care system as a whole.
He remarked that the EU medical device regulation has
inspired other countries and a few days ago at the Inter-
national Medical Devices Forum (IMDF), the Australian
authorities declared that they will align their legislation
to match that of the EU. He is convinced that by work-
ing together we can make a successful transition and
further develop this important sector.
The Key Constraints to Implementation -
A Competent Authority View
John Wilkinson, Director of Medical Devices, Medicines
and Healthcare products Regulatory Agency (MHRA),
United Kingdom, stressed that the implementation of
the MDR should be consistent and fair which was a
problem with the old directives.
John Wilkinson
New responsibilities have been given to competent au-
thorities. New products such as cosmetics and software
will now fall under the scope of the medical devices
regulation, which will present a challenge for everyone
in the system. The new legislation also calls for more
specific responsibility from actors in the supply chain,
which will present some challenges because this supply
chain is global. How were going to manage that sup-
ply chain, he added is going to be critical going for-
ward. Dealing with borderline substances and combi-
nation products in a practical and timely way is also cru-
cial going forward.
He explained that the Competent Authorities for Medi-
cal Devices (CAMD) network and the Commission will
start work over the next 18 months to map out the im-
plications of the implementation process and the EU
work plans which will extend over several years. He re-
minded that the roadmap will be revealed on the 18th of
October at the next stakeholder meeting.
The MHRA has also been mapping the implementation
of the MDR, which is a lot of work for national authori-
ties. There are a number of key constraints to the imple-
mentation of the Medical Devices Regulation, such as
the dual regulatory system during the transition period,
and how people perceive the new CE mark versus the
old CE mark. The whole system will be underpinned by
guidance and it will evolve. The regulations are directly
applicable and Member States have less latitude to in-
terpret things. Eudamed is a critical building block of
the system. If Eudamed is late, he stressed, there need
to be provisions on how this can be handled.
Two groups are underpinning the work on implementa-
tion of the regulation and dealing with these con-
straints: the implementation Task force, an ad hoc
group recently reconstituted looking at what needs to
be done, and the transition subgroup. Work will also
need to be done by expert groups in different areas.
The transition subgroup mainly consists of regulators
and lawyers looking at interpretive legal issues with the
transitional provisions.
He explained that we are transitioning from an old to
new governance structure (the CAMD to the Medical
Device Coordination Group (MDCG)). The MDCG has a
broader role and is currently looking to reduce duplica-
tion in the roles.
On classifications under the new regulation, he ex-
plained that the focus should not be on up or down
classifications, but on the evidence to support clinical
claims. In respect of substance-based medical devices,
he too believes that the old legislation was inadequate.
On clinical evaluations he stressed the importance of
evidence to support risk assessments.
12
 Conference report

In terms of challenges ahead, he explained that it is characteristics which make it unique. He stressed that
about getting clarity through the legal text to give eco- this is particularly relevant for medical devices made of
nomic operators clarity going forward. complex natural substances, whose composition cannot
be generalized and linked to homogeneous product
MDR Implementation and Substance-Based categories. He believes that the application of these two
Medical Devices criteria, combined with a constructive discussion be-
tween European and national regulatory authorities,
notified bodies, industrial associations and companies,
Emiliano Giovagnoni, Regulatory Affairs Director, Abo-
will allow us to face effectively the main criticalities of
ca, presented the industrys perspective on the imple-
the new regulation.
mentation of the MDR. Now that the regulatory frame-
work for medical devices has been defined, he believes
There are many aspects of the new regulation that will
it is important to establish implementation rules able to
have a significant impact on industry and that must be
welcome the innovative character of substance-based
taken into consideration. These include the definition
medical devices.
(article 2) of a medical device, the classification Rule 21
and defining the concept of absorption, clinical prod-
We need to define the rules of the game, in order to
uct evaluations and the role of notified bodies. The solu-
implement the provisions of the new regulation proper-
tion, he explained, can be found by adopting a
ly, he explained. To do this, two main criteria need to
harmonized European interpretative system based on a
be taken into account: a European harmonized interpre-
"case by case" evaluation.
tative system specifically designed for substance-based
medical devices, and case by case evaluations. We
A principal intended action which is achieved by phar-
need a regulatory approach specifically developed for
macological, immunological or metabolic means distin-
substance-based medical devices he explained, which
guishes a medicinal product from a medical device. He
takes into consideration the differences with medicinal
explained that up to now, an approach by exclusion
products. This, he explained can be achieved with a
has usually been followed at regulatory level and a
systematic revision of the guidance documents
product is generally classified as a medical device only
(Meddev, Common specifications etc.). Once the gen-
when there are no medicinal products already regis-
eral interpretative context has been defined, it is neces-
tered, regardless of whether its mechanism of action is
sary that each product is evaluated according to its

13
by pharmacological, immunological or metabolic
means. He therefore believes it is necessary to reassess
all the mechanisms of actions and to assign each of
them either to the category of medicinal products or to
the category of substance-based devices, based on sol-
id scientific data and regardless of their historical classi-
fication. This would ensure a harmonised EU approach,
and avoid inverse shopping legislation, and attempts
to support historical classifications.
Emiliano Giovagnoni
He gave examples of inverse shopping legislation such
as an osmotic/ bulk-forming mechanisms of action for
laxatives, a mucoprotective action for cough syrups and
a bacterial anti-adhesion mechanism of action in prod-
ucts for cystitis. In Abocas view antacids should be con-
sidered as medical devices. Of interest is the osmotic
mechanism of action, a colligative property which de-
pends on the concentration of solute rather than the
structure of the molecule. As there is no receptor-ligand
interaction the mechanism of action should be regarded
as a medicinal product. The definition of
pharmacological means is crucial for the medical de-
vices sector. Meddev 2.1 provides a starting point, but
he believes it needs to evolve, and not introduce the
concept of indirect pharmacological action.
Rule 21 places absorption at the centre of the classifica-
tion system. When absorption is relevant for the intend-
ed purpose the classification is clear. However, all sub-
stance based medical devices, are somehow absorbed
by the human body. In the absence of a clear criterion, a
product containing substances generally recognized as
safe and other active substances absorbed in concentra-
tions not relevant for risk assessment would be classi-
fied in class III without any justification. He believes that
absorption should justify class III only when the sub-
stances absorbed are relevant for the risk assessment.
Aboca proposes for products containing natural sub-
stances to apply metabolomics techniques to evaluate
the extent of absorption. Manufacturers would be able
to assess on a case-by-case basis, if the substances is
absorbed in concentrations relevant for risk assessment,
and then whether the extent of absorption is such that
classification of the product in Class III is required. Oth-
erwise, it should fall into Class IIb.
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 Conference report

Regarding the role of notified bodies, it is necessary to

ensure an efficient system of notified bodies able to
manage the huge number of requests they will receive,
within the timeline of the transitional period, given that
substance-based medical devices currently classified as
class I will seek Notified body certification, and a gen-
eral upgrade of the risk class is foreseen for many sub-
stance-based medical devices. And in Italy alone, more
than 2,000 substance-based medical devices are cur-
rently on the market. A European system of notified
bodies highly specialized in the evaluation of substance-
based medical devices and able to ensure a smooth
transition from the current system to the new one is
critical, he explained.
Bettina Funke

Clinical Evaluations and the Equivalence

Approach She explained that equivalence to another similar device
can be demonstrated from the scientific literature by
taking into consideration the technical, biological or
Bettina Funke, Head of Medical Devices, Scientific &
clinical characteristics of the product.
Regulatory Affairs, R&D Consumer Health Care, Merz
Consumer Care GmbH, presented the industrys view on
Technical equivalence, she explained is the most fea-
the equivalence approach for clinical evaluations. The
sible to demonstrate especially when the device has a
new medical devices regulation introduces stricter re-
similar design, similar conditions of use, similar specifi-
quirements for clinical evaluations. In that context, clini-
cations and properties and similar principles of opera-
cal data, defined under article 2, as information con-
tion and performance requirements. Next would be bio-
cerning the safety and performance of medical devices,
logical equivalence; having the same materials or sub-
can be sourced either from the scientific literature on
stances in contact with the same human tissues or body
similar devices, clinical investigations or post market
fluids for a similar kind and duration of contact and sim-
surveillance.

15
ilar release characteristics. Last would be the clinical
characteristics; having the same clinical conditions or
purpose, severity and stage of disease, same site in the
body and similar population. There is also a require-
ment for manufacturers to have sufficient levels of ac-
cess to the data relating to devices with which they are
claiming equivalence in order to justify their claims.
However, what is deemed sufficient needs to be clari-
fied.
She then gave examples of possible outcomes when the
equivalence approach is interpreted too strictly. One
example was of a nasal spray made from seawater,
where the source of the seawater in the formula was
changed. Another was a simethicone preparation, where
a flavouring excipient was changed. Although these
seem like minor changes the equivalence of both the
nasal spray and the simethicone preparation could be
questioned. However, she believes this general view
doesnt really contribute to the safety and performance
of substance based medical devices. She believes that
instead, a thorough case by case evaluation would be
more meaningful. Moreover, if equivalence cannot be
established a huge number of additional clinical trials
will be required.
She then presented the challenges with performing clin-
ical trials. You need to convince an ethical commission
about the need for a trial for a change in substance hav-
ing no impact on the principal mode of action or for a
longstanding product, and this could be judged as a
repetition of an already conducted trial which would be
unethical. Financial concerns are also an issue. We
may lose a number of good products since high invest-
ment in clinical trials may not be commercially viable for
each individual product. The remaining transition peri-
od lasts for only two and a half years from now which is
extremely challenging for all parties to handle this huge
amount of trials. Substance based medical devices are
at risk of requiring new clinical trials for formal reasons,
she explained and although the legal manufacturer
wants to comply with the new legislation, these safe and
effective products may disappear from the market.

Fostering Market Access for Substance-

Session 3
Based Medical Devices

Moderated by Maud Perrudin, Legal and Regulatory

Affairs Manager, AESGP, this session explored the key
market access issues for manufacturers of substance
based medical devices and the views of representatives
from different notified bodies.

Regulatory Challenges for Notified Bodies

and Market Implications

Roberta Marcoaldi, Director of the Notified Body 0373

-Istituto Superiore di Sanit (ISS), Italy, presented the
challenges of the new Medical Devices Regulation for Roberta Marcoaldi
notified bodies. She explained that in the last few years
the legislation for the medical devices sector has been
The Regulation 920/2013 has involved a re-
subject to a long and complex review process. The revi-
accreditation process of Notified Bodies which has not
sion has become necessary to ensure a high level of
yet been concluded. Some Notified Bodies have been
patient and user health protection. In 2013 the Commis-
unable to demonstrate their ability to respect the new
sion implementing Regulation on the designation and
requirements and therefore the previous designation
the supervision of notified bodies under the Medical
obtained in accordance with the directive 93/42/EEC
Devices Directives was published which proposed new
was withdrawn. This has led to market problems as sev-
requirements for Notified Bodies.
eral manufacturers have been forced, within a relatively

16

short time, to identify an alternative Notified Body for
the CE Certification of medical devices.
In the Regulation 920/2013 some issues concerning the
role and obligations of Notified Bodies were in fact an-
ticipated, and include: the qualification of the personnel,
Quality management system (QMS), the definition of
conformity assessment procedures, demonstration of
the availability of personnel for clinical evaluations,
deepening of the qualification and classification assess-
ment procedures and deepening of the clinical data
assessment procedures including the Post-Market Clini-
cal Follow up (PMCF).
The entry into force of the new Medical Devices Regula-
tion (MDR 2017/745) emphasizes and shows more strin-
gent requirements for notified bodies, manufacturers,
the technical documentation produced by manufactur-
ers, Post-Market Surveillance (PMS) and Post-Market
Clinical Follow up (PMCF). New classification rules have
been introduced, such as the new approach for sub-
stance-based medical devices and medical devices
which contain medicinal substances. The Medical Device
Coordination Group (MDCG) now also plays a role in
the conformity assessment process and re-accreditation
process of notified bodies.
All Notified Bodies must be re-accredited in order to
carry out certification activities in accordance with the
MDR. The timeline for the application of the regulation
is 26 May 2020. All Notified Bodies will have to submit
their application for the new designation in the coming
months. She explained that the Italian competent Au-
thority has already asked the Italian Notified Bodies to
express their intention to re-designate and to indicate
the period during which the application will be submit-
ted.
A draft list of NBOG codes (types of devices for the pur-
pose of specifying the scope of the designation under
the Regulation (EU) 2017/745) has been published. A
draft application form (for designation as notified body
under the Regulation (EU) 2017/745) is expected to be
published by the end of November 2017. Then the Noti-
fied Bodies will be able to submit their application for
designation by December 2017 / January 2018.
We are very concerned because the re-accreditation
process will be very articulate and surely quite long (up
to 20-24 months) for assessment purposes, because a
number of different assessments steps are required: a
preliminary assessment report of the authority responsi-
17
Conference report
ble for notified body, assessment by the Commission
and the Medical Device Expert Group, appointment of
the joint assessment, audit on site (on site assessment
of applicant body), follow up activities (report of joint
assessment and authority responsible for notified body).
Then the MDCG will deliver its recommendation and a
decision will be taken on the designation of Notified
Body. The re-accreditation process will also be followed
by the notification of the designation (which might take
another 3 6 months).
She believes that the harmonization of conformity as-
sessment procedures has not yet been achieved, in par-
ticular for: unannounced audits (are notified bodies
forced to submit a three year plan and not five as per
the MDR?), clinical evaluations (are notified bodies
forced to apply the guideline that underlines the princi-
ple of equivalence; MEDDEV 2.7.1 rev. 4?), personnel for
clinical evaluation (are notified bodies forced to demon-
strate a clinical expertise for personnel that carry out the
clinical evaluation?) and medical devices containing me-
dicinal substances .
The MDR 2017/745 establishes the qualification of sub-
stance-based products and defines a special classifica-
tion rule: 21. MDR requirements also define a more
stringent approach to assess such medical devices. This
represents a new challenge for Manufacturers and Noti-
fied Bodies. Substance-based medical devices will no
longer be classified in class I. This will mean an in-
creasing number of medical devices requiring the evalu-
ation of a Notified Body, and the development of spe-
cific know-how will be necessary, in particular for Noti-
fied Bodies.
Rule 21 introduced the concept of substances absorp-
tion. In this respect, she believes it is necessary to define
a correct interpretation of rule 21 and understand the
term absorption of substances, as the absorption of
substances can determine the classification of medical
devices.
In addition, the quality and safety of devices that are
composed of substances or of combinations of sub-
stances that are intended to be introduced into the hu-
man body via a body orifice or applied to the skin and
that are absorbed by, or locally dispersed in, the human
body, shall be verified where applicable and only in re-
spect of the requirements not covered by this Regula-
tion, in accordance with the relevant requirements laid
down in Annex I to Directive 2001/83/EC for the evalua-
tion of absorption, distribution, metabolism, excretion,
local tolerance, toxicity, interaction with other devices,
medicinal products or other substances and potential
for adverse reactions.. The notified body shall seek a
scientific opinion from one of the competent authorities
designated by the Member States in accordance with
Directive 2001/83/EC or from the EMA on the compli-
ance of the device with the relevant requirements laid
down in Annex I to Directive 2001/83/EC. The opinion of
the medicinal products authority consulted shall be
drawn up within 150 days of receipt of all the necessary
documentation. The notified body then has to consider
the views expressed in the scientific opinion. Manufac-
turers will therefore have to provide documentary evi-
dence in the product technical documentation for Sub-
stance based medical devices.
All manufacturers are also required to establish and up-
date a clinical evaluation plan to demonstrate conformi-
ty with safety and performance requirements. Clinical
evaluations may be based on clinical data from an
equivalent medical device. However, the demonstra-
tion of equivalence is very difficult for manufacturers.
As a notified body, she plans to support the manufac-
turer during the transitional period. The manufacturer is
also required to proactively collect and evaluate clinical
data (Post-market Clinical Follow up (PMCF)) to confirm
the safety and performance of the medical device
throughout its expected lifetime. It is a continuous pro-
cess which updates the clinical evaluation and should be
addressed in the manufacturer's post-market surveil-
lance plan.
Rule 14 on medical devices incorporating a medicinal
substance requires that the quality, safety and useful-
ness of the substance be verified with the methods
specified in Annex I to Directive 2001/83/EC. Notified
bodies must then verify the usefulness of the medicinal
substance and seek a scientific opinion from a compe-
tent authority or EMA on the quality and safety of the
substance including the benefit or risk of the incorpora-
tion of the substance into the device. Under the old
Medical Device Directive, the notified body could take
the updated scientific opinion into account in reconsid-
ering its assessment of the conformity assessment pro-
cedure. Under the new medical device regulation, the
notified body cannot deliver the certificate if the scien-
tific opinion is unfavourable and shall convey its final
decision to the medicinal products authority consulted.
She concluded by describing how Notified Body 0373
are preparing themselves for the application of the
MDR. We will submit our application in the first three
months of next year, then we will carry out the new
qualification of personnel taking into account new Noti-
fied Body Operations Group (NBOG). We will also review
our quality management system and conformity assess-
ment procedures. The certification process will also be
reviewed considering the change of the MDR (role of
Medical Device Expert Group, new consultation proce-
18

dures with the competent authority for medicinal prod-
ucts). Notified Body 0373 will also organize information
and training events for manufacturers.
On the next steps forward, she explained that there
should be discussions with the authority responsible for
Notified Bodies on a harmonised approach to imple-
mentation. Updates should be shared between the No-
tified Bodies and manufacturers to foster closer collabo-
ration, and discussions at European level (Medical De-
vice Coordination Group, common specifications, imple-
menting acts) should be followed.
Getting Ready for The New Medical Device
Regulation
Jeff Vest
Jeff Vest, Principal Scientist at TV SD UK, a notified
body in Germany, began his presentation by giving an
overview of the timelines of the MDR since the Commis-
sion consultation on the medical devices framework in
2008. Eudamed will need to be functional by March
2020. There are confidentiality requirements which ap-
ply by May of 2018. A lot of manufacturers dont have
the information to meet the MDR. Some class 1 medical
devices will be up-classified. Annex 4 of the Active Im-
plantable Medical Devices Directive (AIMDD) and Annex
4 of the Medical Devices Directive (MDD) (for the self-
certification by manufacturers) will become void by 27
May 2022. Certificates issued from May 25 2017 shall
become void at latest on 27 May 2024, although devices
may continue to be made available or put into service
until the 27th May 2025. From May 2020, there should
be no significant changes in the design and intended
purpose of the device. The reporting of serious adverse
events and device deficiencies as per the MDR also ap-
19
Conference report
plies from May the 26th 2020. Finally, the co-ordinated
assessment procedure on clinical investigations shall
apply from May the 26th 2027.
The labelling system and whether this will be similar to
the FDA approach has yet to be defined. UDI (Unique
Device Identification system) is a costly process. he ex-
plained, We need to implement an acceptable model
and in the regulatory world there isnt enough time to
do this.
Consultancy services cannot be offered by notified bod-
ies but TV SD can do mock reviews and offer Gap
analysis services. Ultimately though, it is up to industry
to fill those gaps. In-house trainings offered by TV
SD are generic and cant be tailored for companies.
TV SD also organise workshops and throughout the
transition period they anticipate a high demand for clin-
ical workshops. They can also offer mock audits, clinical
audits etc. They can review the manufacturers clinical
evaluation report, technical documentation, Periodic
Safety Update Reports (PSURS), and they will consider
justifications for not doing a PMCF (Post Market Clinical
follow-up).
He indicated that TV SD is looking forward to the
joint audits by the competent authorities. An uncertain-
ty that remains is whether notified bodies can cope with
the flood of applications. When will notified bodies be
appointed? All in May of 2020, or will it be a staggered
appointment? The MDR is untested so some changes
can be expected from unintended consequences or in-
terpretations of the legislation. There are still uncertain-
ties remaining relating to UDI, and common specifica-
tions (which have not yet been published).. There are a
number of key elements that are still missing, he ex-
plained. He concluded by inviting industry to discuss
updates and meet early with their notified body, so they
can advise manufacturers on what needs to be done to
meet the requirements of the MDR.
The Medical Device Regulation and The
Uncertainties That Lie Ahead
Jrg Wilke, from Zertifizerungsgesellschaft fur Mediz-
inproduckte Europa (ECM), opened his presentation
with an introduction of his notified body, CE 0481. ECM
0481 is a notified body under the Medical Devices Di-
rective (MDD) since 1995. They lack laboratory capaci-
ties and focus on quality assurance and access. Their
scope is limited to mainly non-active medical devices
covering sterile products, animal tissue products and
pharmaceutical active substances. They have experience
with substance based medical devices. They are the
third notified body to undergo joint assessments.
He explained that notified bodies are facing an increas-
ing number of applications due to the decreasing num-
ber of notified bodies and reclassification due to the
new MDR. In this respect, he welcomed input from in-
dustry. He then described the extent of assessment ac-
tivities carried out by the notified body. There are audit
activities at the premises of the legal manufacturer and
critical suppliers, if necessary, and due to the reclassifi-
cation there will be increased technical file assessments.
A scrutiny and consultation process is now required de-
pending on the nature and classification of the medical
device. Physical product testing during notified body
audits is required, and for certain products there are
periodic review obligations, not covered by the current
legislative framework. All classes apart from sterile class
I or class I a measuring function will require technical file
assessment activities. These are case driven for class III,
but for the other classes it will be based on a repre-
sentative sample. However, currently there are no crite-
ria in the MDR of what a representative sample means.
The NBOG guidance for audits and testing of repre-
sentative samples will no longer be applicable, and
there may be a potential implementing act by the Com-
mission concerning the legal requirements for the test-
ing of samples.
He explained that clarity is needed for the classification
rule 14 for medical devices with medical substances an-
cillary to the device, replacing the current rule 13, rule
19 for nanomaterials and rule 21 on substance-based
medical devices.
Rule 14 refers to medicinal substances with an ancillary
action to a medical device but have no clear action on
the human body. The rule has led to discussions over
whether the function as a preservative would affect its
classification. Clarification is also required on whether
rule 19 for nanomaterials is based on the nanomaterial
or its intended use.
Jrg Wilke
For rule 21 on substance-based medical devices, does it
apply to the all substances or those achieving the princi-
pal intended action of the product? There is no defini-
tion of substance in the medical device legislation, and
the legislation doesnt refer to definitions in the legisla-
tion for pharmaceutical products. In respect of Rule 21,
there are different perspectives on what is inside the
body. From a biological perspective, he added the
stomach is outside the body. Moreover, absorption re-
quires crossing a barrier to be distributed locally or sys-
temically-therefore the terms locally dispersed and sys-
temically absorbed need to be clarified and are mislead-
ing.
He stressed that requirements/guidance is required for
the new classification rules, which the current guidance
doesnt address. At national level, NAKI in Germany, a
co-ordination group has been established located at the
ministry of health, to address these questions. They are
mirroring the competent authority meetings quite well,
and some of its subgroups might be present in the
forthcoming Medical Device Co-ordination Group
(MDCG) which has not been established yet. We need
more consensus at EU wide level to allow a homoge-
nous interpretation of fundamental questions so that
manufacturers can apply properly the classification rules
and notified bodies can check these procedures.
20
 Conference report

A Business Perspective to Foster Market product. He asked what the sense of this reclassification
Access for Substance-Based Medical Devices was and whether there had been an impact analysis.
Indicating that his company had carried out its own im-
Maikel Hendriks, CEO of Medical Brands, began by pact assessment, he presented the results that a third of
giving an overview of the history of his company, look- OTC medical devices on the EU market could be subject
ing at dental products before moving to the self-care to such reclassification.
sector. Their product portfolio includes feminine prod-
ucts, cough and cold products, footcare etc. and many
different formulations are marketed. Although their first
product Freeze off your Wart was seen as a medical
device by notified bodies and the competent authority,
when it came to market, concerns were raised by the
competent authority because it involved bringing home
treatment people received at the doctor. He firmly be-
lieves that innovation should come before regulation.
He alluded to the blue guide book which was created to
remove technical barriers to EU trade and to enable the
free movement of safe goods. He now believes that
technical barriers to innovation, particularly in self-care Maikel Hendriks
are being created.

Today healthcare is moving closer to the user with mo-
bile apps, the internet, on-line pharmacies, wearables
etc. which will lead to less interaction with GPs and con-
venience for products.
Regarding substance-based medical devices, although a
physical mode of action was described for Simethicone
in the reputed opinion by the competent authority, the
product was subsequently classified as a medicinal
Eudamed, the lack of guidance and clinical equivalence
are issues which industry faces going forward. On Noti-
fied bodies, he explained that we now have 58 notified
bodies; when we started, there were 85. In the mean-
time, 16 were withdrawn, 9 expired and 2 were suspend-
ed. Further reduction can be expected with the designa-
tion procedure. After discussions with the Commis-
sion, the first notified body will set the standard and
there is a risk that other notified bodies will not pass
The first MDR audits start in May 2020.

21
He also alluded to the change in the role of the author-
ised representative from a mailbox function to responsi-
bility for parts of the manufacturers dossier. On adver-
tising, Neprofarm, the self-care association in the Neth-
erlands, have developed an advertising code of conduct
for medical devices, which, through the work of PAGB,
will be mutually recognised by the UK.
Authorities should go through the manufacturers dos-
sier, rather than group products based on opinions from
EMA. He calls for case-by-case reviews of products.
This will allow self-care to grow, and allow innovative
products to remain on the market. Otherwise, he ex-
plained, we can create a road-block if we see patients as
incapable of managing their own health.
AESGPs Priorities and Ongoing Work
Maud Perrudin, Legal and Regulatory Affairs Manager
at AESGP, presented AESGP priorities with the imple-
mentation of new Medical Devices Regulation. The leg-
islation is a great achievement, she remarked however,
the implementation will be a challenge. We are a sci-
ence based industry, she explained, and hopes that the
implementation will be science based. In implementing
the text, she calls for transparency and a proportionate
and uniform approach. AESGPs key priorities include
transitional measures, the regulatory status of products,
the quality and safety evaluation of substance based
medical devices, and the resource/capacity of notified
bodies.
Maud Perrudin
A number of Class I devices will be up-classified to
class IIb or from class IIb to class III and there will be
many new requirements to comply with notably for the
up-classification to class III (including new clinical inves-
tigations). In this regard, she believes that reclassifica-
tion should start with a case by case assessment of all
the characteristics of the product. She believes medical
devices should be regarded holistically, and should they
contain substances known to have pharmacological,
immunological and metabolic properties, the only way
to rule out the medical device classification is to scien-
tifically establish that the substances do exert such
properties in the product as formulated and that such
properties plays a role in achieving the principal intend-
ed action of the product. Core to the business of AESGP,
is proper definitions of pharmacological, immunological
and metabolic means which is still on the Commissions
agenda.
The so-called rule of doubt set in Article 2.2 of the Me-
dicinal Products Directive 2001/83 applies, provided
that the concerned product meets both definitions of a
medicinal product and of medical devices, and results in
the products classification under the medicinal prod-
ucts directive. Oftentimes, she remarked, if a product
looks like a medicinal product it is classified as such.
When there is certainty that the product is classified as a
medicine in the first place, she believes that national
authorities must still demonstrate scientifically that the
product is medicinal by function (which means that it
achieves its action by pharmacological, immunological
or metabolic means in line with the Hecht Pharma Court
Case, C-140/07, 29). Therefore, proper definitions of
pharmacological, immunological or metabolic means
are critical.
She highlighted the issues with determining regulatory
status under the medical devices regulation, such as the
transparency of the Helsinki procedure, which is mainly
dedicated to the national competent authorities with
input from stakeholders far too late in the process. She
is hoping this will improve under the new legislation,
and that AESGP can provide data before a classification
decision is taken. Although Article 4 under the MDR will
be useful to clarify the regulatory status of Medical de-
vices, she calls for a clarification of the consultative role
of EMA, EFSA and ECHA in the determination of the
products regulatory status, the proper involvement of
notified bodies and concerned manufacturers at an ear-
ly stage and a call for data on a category of products
published on the Commission website prior to the
launch of the procedure.
In respect of substance-based medical devices, she indi-
cated that AESGP is doing its homework developing
22

guidance on the implementation of Rule 21, including a
decision tree to help manufacturers in borderline cases
also with Rules 4, 5 and 19. For quality and safety evalu-
ations, she stressed that concept of generally consid-
ered as low-risk should apply to substances with a long
history of safe use (e.g. as foodstuffs) or that have been
scientifically reviewed by European scientific bodies/
committees.
The implementation of Rule 21 should be proportion-
ate and risk-based. She stressed that the classification
must always be justified by the intended purpose and
the inherent risk. The interpretation of Rule 21 also
needs to take into account the various linguistic ver-
sions and the overall context of the medical device reg-
ulation.
23
Conference report
Referring to the previous presentations, she highlighted
the concern of the self-care industry regarding contin-
gencies with the notified body designation process and
their capacity to meet the new requirements of the reg-
ulation. She believes that we should organise collabora-
tion with Notified Bodies and foster dialogue with na-
tional competent authorities and Commission to devel-
op guidance for Notified Bodies and authorities and
share good practices and expertise. AESGP is happy to
share its experience and knowledge with notified bodies
and competent authorities.
She concluded by emphasising that the implementation
needs to make the MDR and its Rule 21 useful in order
to achieve its objectives.
 Creating a Proportionate Regulatory
Session 4
Environment for Herbal Medicinal Products
Herbal Medicines Are Widely Appreciated
By European Citizens
Karin Kadenbach, Member of the European Parliament
Committee for environment, public health and food
safety (ENVI) (MEP) since 2009, presented her views on
herbal medicinal products in a video message. Herbal
medicines are widely appreciated by European citizens,
she explained. 80% of the population have used herbal
medicines, according to various surveys. The European
Parliament was instrumental in the establishment of the
Herbal Medicinal Products Committee (HMPC) at the
European Medicines Agency (EMA), as part of the Di-
rective on Traditional Herbal Medicinal products adopt-
ed in 2004, she explained. Since then the committee
has delivered notable results, in particular with regard to
establishing monographs for herbal medicinal plants,
benefiting both patients and manufacturers. She be-
lieves that the work of the HMPC will be important in
the future, in light of the interest of European citizens in
these products. She also hopes that the work of the
HMPC will not be negatively affected by Brexit and the
relocation of the EMA. Manufacturers of herbal medi-
cines operate in a competitive environment, and many
products have a lower turnover rate and higher admin-
istrative costs than comparable products. She concluded
by welcoming the timely discussions on creating a pro-
portionate regulatory environment for herbal medicinal
products.
Karin Kadenbach
Challenges With Traditional Use Registra-
tions
Agns Mathieu-Mendes, Deputy Head of Unit, Direc-
torate Health and Food Safety, European Commission,
shared her reflections on the challenges with traditional
use registrations for Herbal Medicinal Products
(THMPs) Herbal medicines can be authorised on the
basis of a full marketing authorisation application, a bib-
liographic one or registered on the basis of safety and
plausible level of efficacy attested by a long history of
use (30 years including 15 years in the EU) under the
Traditional Herbal Medicinal products Directive
2004/24/EC. The Commission endorses the EMA scien-
tific assessment with regard to the list of herbal sub-
stances, preparations and combinations thereof for use
in traditional herbal medicinal products (Commission
Decision 2008/911/EC). The list has recently been en-
riched with two new list entries: Sideritis herba and Va-
lerianae radix.
Agns Mathieu-Mendes
Herbal products can be marketed as medicine or food
and the responsibility of the classification lies with
Member States based on the presentation and claimed
effect. This has led to disparity at national level with the
uptake of the traditional use registration scheme. On
this note, she referred to the on-going REFIT evaluation
for the Regulation on health claims legislation; the out-
come of which is needed before to take any steps to-
wards a potential change of the herbal legislation which
is for the moment seen as fit for purpose.
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Traditional and Herbal Medicinal Products:

Harmonisation and Globalisation

The work of the EMA Committee on Herbal medicinal

products was illustrated by Werner Knss, Head of Di-
vision, complementary and Alternative Medicines and
Traditional medicines, Federal Institute for Drugs and
Medical Devices (BfArM) as well previous Chairman of
the EMA Committee for Herbal Medicinal Products
(HMPC). One thousand six hundred registrations were
granted over the past years but recently a couple of
new herbal medicinal products were authorised based
on a full Marketing Authorisation Application (MAA):
Episalvan through the centralised procedure and a
green tea extract (Veregen) and Cannabis extract via the
decentralised procedure (DCP). The outputs of the
HMPC fostered harmonisation and mutual understand-
ing of authorities paving the ways to these DCP and Werner Knss
centralised authorisations.

The International Regulatory Cooperation for Herbal

Global harmonisation is also key for companies which
Medicines (IRCH) now under the harbour of WHO; has
seek to export due to the diversity of the regulatory
been an important step towards promotion of best reg-
frameworks across the world. The EMA released a Ques-
ulatory practices on herbal medicines, although it will
tion and Answer document for companies outside the
take some time to develop this platform and find ways
EU want to meet EU regulatory requirements for
how to converge the different regulatory systems.
(traditional) herbal medicinal products.

25
Contribution of The European Pharmaco-
poeia to A Proportionate Regulatory Envi-
ronment for Herbal Medicinal Products
After the safety and efficacy pillars addressed by the
previous speakers, Susanne Keitel, Director, European
Directorate for the Quality of Medicines & Healthcare
(EDQM), addressed the quality one and the important
role the European Pharmacopoeia and its general chap-
ter and monographs play in that regard.
Susanne Keitel
There are 6 general monographs and 294 individual
monographs dedicated to herbals. The EDQM has also a
number of specific monographs dedicated to Tradition-
al Chinese Medicine (TCM) to prevent severe quality
issues (false identification, adulteration, contamination
with pesticides).
She described some current challenges in the TCM field
such as the availability of samples which are required for
monograph elaboration. These include commercial
samples, authentic reference samples (to confirm that
commercial samples are both genuine and of an ac-
ceptable quality) and reference samples of substitute/
adulterant herbal drugs (for exclusion tests) are re-
quired.
Although processing may reduce toxicity and improve
the stability of TCM drugs, does it lead to an enhance-
ment of activity? There are no uniform processing
methods. Regional differences exist in China, for exam-
ple.
Finally, the choice of markers for assays may not always
be indicative of quality, stability or activity. A pilot phase
using semi-quantitative HPTLC has started. This allows
for the determination of one or more markers and the
possibility to use reagents instead of reference stand-
ards.
She also addressed the very controversial issue of pyr-
rolizidine alkaloids (PAs) contamination detected in
herbal medicinal products and food. PAs have been
isolated from 350 plant species, including a number of
weeds. According to HMPC investigations the problem
cannot be solved by simply focusing on Good Agricul-
tural and Collection Practices. EDQM has been given a
mandate to draft a general methods chapter in the field
of pyrrolizidine alkaloids, and maintain a list of PAs
which may be covered by the general chapter.
The Views of Industry on Herbal Medicinal
Products
Finally the views of the herbal medicinal products indus-
try were presented by Christelle Anquez-Traxler, Reg-
ulatory and Scientific Affairs Manager, AESGP, who
highlighted that the Directive 2004/24/EC and the crea-
tion of the HMPC within the EMA were milestones in the
regulatory system for herbals. The EU herbal mono-
graphs foster harmonisation and facilitate registrations.
However, industry would like an increased acceptance
of well-established use and paediatric use indications in
EU monographs and more entries making it to the list.
The threshold for acceptable genotoxicity data should
not become so high that no further list entries can be
finalised. In respect of paediatric use indications, paedi-
atric research in herbals should be stimulated, encour-
aged and rewarded in Europe. Research is very costly
and it is difficult to recoup investment but clinical trials
may not always be needed. Registries, real-world data
or extrapolation may provide opportunities. To improve
the functioning of the system and the sustainability of
the herbal medicinal products sector, the following are
needed by the industry:
Respect of community monographs. A survey con-
ducted by AESGP in 2015 found that more than half
of granted marketing authorisations/registration
(based on monograph) deviate from the monograph
for various reasons. The acceptance and relevance of
EU Monographs is still very heterogeneous across
Member States. Generally there is a higher ac-
ceptance of THMPs monographs compared to well
established use (WEU) monographs. The main areas
of deviation are the indications, age limits, and pre-
clinical safety data.
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 Conference report

Assessment time in line with legislation. Currently This will ensure that the herbal medicinal products sec-
review timelines for THMPs are still extremely long, tor can remain competitive and safeguard innovation in
taking up to 3 years (based on an AESGP internal herbal medicines.
survey).

Fees proportionate to work going into the evalua-

tion. Fees should distinguish between Marketing au-
thorisations with or without a monograph as the pre-
clinical/clinical assessment would already be done by
the HMPC.

Resources and expertise on herbal medicines needed

within national agencies.

Simplified maintenance of herbal medicines taking

into account their known safety profile (simplified
variations). Currently any manufacturing change for a
herbal is considered a major variation. AESGP recent-
ly presented a proposal to the Regulatory Optimisa-
tion Group (ROG), a HMA subgroup focused on reg- Christelle Anquez-Traxler
ulatory/business optimisation, on the simplification
of the variation classification for herbal medicines.

Invitation to the Next AESGP Meetings

At the end of the conference, AESGP Director General, Dr Hubertus Cranz, invited participants to attend the next
AESGP meetings in Lisbon on the 26th-27th of February 2018, with the Heads of EU Medicines Agencies, and the 54 th
AESGP Annual Meeting in Amsterdam on the 5th -7th of June 2018.

27