AESGP Euro OTC News

Issue 259 | 20 June 2014

Medicines

Pharmacovigilance

▪ PRAC April Meeting Minutes 13

▪ Updated EURD list 13

▪ PRAC June Meeting Minutes 14

▪ NtA - Revised Chap 3 Vol. 2A 14

Clinical trials

▪ EMA policy on CT data transparency 14

▪ EMA policy on CT data agreed 15

▪ CT Regulation published in the OJ 15

▪ EMA meeting on IT platform 16

Art. 57(2) / XEVMPD

▪ Updated XEVMPD controlled vocabularies 16

Pharmacopoeia

▪ Report of Annual meeting of National

Pharmacopoeia Authorities 16

CMDh

▪ Updated list of substances under

PSUR Work Sharing Scheme 17

▪ CMDh May Report 17

EMA

▪ EMA revised Q&A related to

pharmacokinetic matters 18

▪ EMA CHMP May Meeting Highlights 18

▪ Sir Kent Woods reelected in EMA MB 19

▪ EMA MB March Meeting Minutes 19

▪ Final QP declaration template + Guidance 20

ECJ

▪ Final QP declaration template and Guidance 20

▪ Cases C-358/13 & C-181/14 21

Guidelines for comments

▪ AESGP comments on Q&As 21

▪ Draft guide on monitoring of

medical literature 22

▪ ICH Q7 Q&A for comments 22

▪ WHO draft monographs on Pyrantel 23

▪ WHO Storage and Transport

Technical Supplements 23

Herbal news

▪ EMA HMPC May Report 23

▪ Final CM on Ginseng radix 24

▪ Draft CM Agrimoniae herba 24

▪ Final CM on Ononidis radix 25

▪ Rev. CM on Thymi herba 25

▪ Final PS on Andrographidis paniculatae folium 25

Herbal (medicinal) products, food supplements, self-care medical devices

Paving the way towards a coherent system

Brussels, 7-8 October 2014 | aesgp.eu/BRU

Conference

See conference programme on page 26. Registrations now open on the conference website.

50th AESGP Annual Meeting | 18th WSMI General Assembly

Conference report on pages 3-12

2 AESGP Euro OTC News | Issue 259

Euro OTC News

Monthly news update by the Association of the European Self Medication Industry

Self-care: the first choice in health care 7 avenue de Tervuren, 1040 Brussels, Belgium Tel.: + 32 2 735 51 30 Fax: + 32 2 735 52 22 E-mail: info@aesgp.eu http://www.aesgp.eu

AESGP © 2014 | All rights reserved

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Food

Medical devices

Food supplements

▪ Commission regulation on methods of

sampling of FS for citrinin published 27

EFSA

▪ AESGP participates in EFSA Stakeholder

Consultative Platform Meeting 27

Health claims

▪ EFSA opinions on health claims 28

▪ Public consultation on EFSA draft Guidance

on Statistical Reporting 28

Food additives

▪ EFSA statement on a conceptual framework

for food additives re-evaluation 29

▪ EFSA statement on an exposure assessment

of Brown HT (E 155) 29

EFSA

▪ Directive on labelling honey published 30

▪ Public consultation on EFSA draft

Scientific Opinion 30

▪ New titles and references of

harmonised standards 31

▪ Revision of the harmonised

standard ISO 14155:2011 31

▪ Council of the EU’s discussion on the

proposed regulation on medical devices 31

▪ European Commission’s Expert Groups and

Working Groups 31

3

Self Care -

the Gold Standard

in Healthcare

50th AESGP Annual Meeting | 18th WSMI General Assembly

London | 3-5 June 2014

Meeti

ng

repo

rt

UK Health Minister Earl Howe highlighted the UK

Government’s support for self care. He pointed out that

with the right regulatory framework and support from

General Practitioners and pharmacists, people are

empowered and enabled to take more responsibility for

their own health.

“The rest of the world often looks to the UK and what we

are doing for adapting their practices,” he said. The

Minister highlighted the UK Medicines and Healthcare products Regulatory Agency’s (MHRA) new,

streamlined classification guideline which focuses on benefit/risk analysis, early discussion with the

regulators and early engagement with stakeholders. The PAGB and MHRA continue to look at how to

incentivise the industry to produce innovative OTC medicines, added the Minister.

UK at the forefront of self-care support

EU Commissioners emphasise value of self-care

European Commissioners for Health and Consumer Affairs,

Tonio Borg and Neven Mimica, honoured AESGP on the

occasion of its 50th

anniversary by addressing the more

than 400 attendees of the event and praising the work

done by the association in the past years.

Commissioner for Consumer Affairs Neven Mimica said

that “the last five decades have seen an evolution in the

use of self-care.” He attributed the growing interest in self-

care mainly to three factors:

‒ people are paying more attention to their health

‒ new needs are created for the ageing society

‒ healthcare has to be delivered with scarce financial and

human resources

Health Commissioner Tonio Borg noted that self-care is

“the first step and first choice in healthcare.” The European

Commission, said Commissioner Borg, is therefore keen to

support patient empowerment.

Tonio Borg

The Rt Hon Earl Howe

Neven Mimica

4

Ageing populations, soaring global healthcare

costs and rising numbers of informed,

empowered patients mean that there has never

been a better time to be in the self care sector,

leading industry figures pointed out at the

meeting.

“The world is getting older, larger and sicker,”

said Novartis CEO Joe Jimenez. Estimates

suggest that there will be one billion more

people on the planet in the next 10 years, over

half of whom will be aged over 50, and by 2025,

the percentage of the world’s population aged

over 60 will have doubled to 20 per cent, he said. With this rise will come a vastly increased disease burden,

with chronic, non-communicable diseases such as diabetes and dementia accounting for 70 per cent of

total global disease in 2025, up from 60 per cent today.

While this might seem bad news for governments, healthcare systems and payers worldwide, it could also

herald an era of unprecedented healthcare advances, fuelled by the willingness of payers - both

governments and consumers - to pay for innovations which will truly change lives.

This is the time of the engaged, informed and empowered consumer. Opportunities for self-medication and

self care companies will be unprecedented. Those companies with innovation power will have the most to

gain from these opportunities. They will be able to produce real breakthroughs for unmet medical needs,

operating on a global scale and serving emerging market consumers as well as those in developed markets.

This is the time of the engaged, informed and

empowered consumer

Joe Jimenez,

The global OTC market was worth an

estimated 86 billion euros in 2013,

growing at an annual rate that outpaced

that of pharma. However, this strong

growth was driven by the phasing of the

cough/cold season, while the results for

the full winter season are expected to be

less positive, Andy Tisman, Senior Principal

at IMS Health, noted at the conference.

Volume growth is limited in many regions,

so innovation could be key, said Tisman.

OTC market growth still outpacing pharma’s

5

How AESGP

and WSMI are

moving things

forward

A major achievement of AESGP

has been getting all

stakeholders involved in

creating a context in which the

industry can create value for

EU consumers and society, said

the Association’s president,

Hans Regenauer. It is very

important to communicate the

evidence for the added-value

of self-medication, stressed

Regenauer.

Zhenyu Guo, Chair of WSMI,

pointed to the importance of

placing OTC medicines within

the broader scope of self-

medication, and discussed the

risk/benefit model for

prescription to OTC switches,

which the organisation has

supported.

He also pointed out that 75

per cent of non-communicable

diseases are preventable,

which presents major new

opportunities for the industry,

in terms of helping people

avoid these conditions through

self-medication, food

supplements and devices.

Rakesh Kapoor

Self-medication not just for

minor ailments

OTC innovation has to focus on creating “big, bold advances that

make a real, meaningful difference to consumers’ lives,” and not

“endless tinkering around the edges,” urged RB CEO Rakesh

Kapoor.

Mr Kapoor argued that while innovation needs new molecules and

ingredients, it really is about people, particularly mothers: “We have

to ask: what do mums want? Do they need their family’s pain relief

to be faster acting or longer-lasting? Or do they want a single dose

that works faster and longer?”

He urged delegates to “develop a consumer-centric mindset” and

“remember, self-medication is not just for minor ailments.”

Meeting report

Hans Regenauer, Zhenuy Guo. Andrew Ward, Financial Times, moderated the discussion.

6

AESGP

social media

guidance

“We can’t ignore the new

healthcare paradigm, and

consumers’ desire to self-

treat is a right we should

support,” noted Roger

Scarlett-Smith, President of

GSK Consumer Healthcare,

Europe in a session chaired

by Briain de Buitleir, PGT

Healthcare CEO.

“Brands must be visible on

social media; providing high-

quality content and trust in

our brands is essential,” said

Scarlett-Smith.

To this end, AESGP has

published a new guidance for

the industry on engaging

with social media.

Considering that many in the

sector face uncertainty about

entering the digital arena, the

guidance will enable

responsible and trusted two-

way communication to

support self-care.

“The guidance is intended for

use by local associations in

the possible development of

national guidelines, and it is a

call to action for the

industry,” said Jeff McDowell,

head of global

communications at PGT

Healthcare. “Open a dialogue

– first listen and then

engage,” he advised, adding:

“The conversation will

We need to rethink the importance

of Rx-to-OTC switches, as they repre-

sent a win-win-win for consumers,

public health and healthcare systems,

said Vincent Warnery, Senior Vice

President at Sanofi’s Global Consum-

er Healthcare division during a panel

discussion on industry-led innova-

tion. For consumers, Rx-to-OTC

switched products provide access to

safe, effective products, and timely

relief of symptoms. The benefits for

public health include a reduced

disease burden and taking advantage

of the key role of pharmacists.

Finally, healthcare systems gain fi-

nancially from the transfer to out-of-

pocket payments by patients, fewer

doctor visits and faster access related

savings, said Mr Warnery. Neverthe-

less, few products have received EU

wide switches. Warnery called for

Switches: a win-win-win

Advertising and self-regulation

Roger Scarlett-Smith, Jeff McDowell, Jaume Pey and Briain De Buitleir

A case study from Spain on the devel-

opment of a self-regulatory frame-

work for the advertising of non-

prescription medicines was presented

by the Executive Director of the Spa-

nish self-care industry association,

anefp, Jaume Pey.

Pey described the various stages

through which the regulatory envi-

ronment evolved in Spain and the

role anefp played in building trust

with the regulatory authorities and

undertaking increasing responsibili-

ties in the advertising control system.

Following the establishment of mutu-

al understanding and the recognition

of all actors’ commitment in ensuring

the accuracy of information commu-

nicated to citizens, the consequent

move to a self-regulatory environ-

ment was a natural development,

noted Pey.

Pey said that the Spanish experience

could easily be transferable to other

countries and encouraged industry to

engage in an open dialogue with

authorities to build trust.

7

Meeting report

new initiatives and incentives to

facilitate the process, for example

“conditional switches”, and the

provision of extended data protec-

tion for significant clinical studies.

Guido Rasi, Executive Director of

the European Medicines Agency

(EMA), urged companies to use the

new opportunities for earlier en-

gagement with EU regulatory au-

thorities to establish the require-

ments needed for a “switch path-

way” for a product, early in its

lifecycle.

All EU health systems are different,

and the UK has been at the fore-

front of switches, in part because

the country relies to some degree

on pharmacy supervision that is not

necessarily the case around Europe,

said Ian Hudson, Chief Executive of

the Medicines and Healthcare

Products Regulatory Agency

(MHRA). “UK takes a liberal ap-

proach, where it is safe to do so,”

he added.

Member of the European Parlia-

ment Dagmar Roth-Behrendt point-

ed out regulation’s role in provid-

ing “an equal framework and foot-

ing” to industry and citizens, point-

ing out that unnecessary re-

strictions should be avoided.

Andy Tisman, Ian Hudson, Dagmar Roth-Behrendt, Guido Rasi, Vincent Warnery and Andrew Ward

Promoting innovation - case studies

To encourage industry innovation, the right incentives

need to be in place. However, different approaches may

often be required for countries with different regulatory

systems and national health priorities. Case studies were

presented in a session chaired by Deon Schoombie,

ASMI Executive Director.

Natalie Gauld, a former member of the New Zealand

Medicines classification Committee who analysed the

enablers and barriers to switches around the world

presented some of the key findings of her research

work.

The support of Government, regulators and stakehol-

ders has made the UK a world leader in switches, while

in the US and Japan, the introduction of three years’

market exclusivity has proved successful, she added.

Japan has a rapidly ageing population, and to alleviate

some of the pressures on the healthcare system, self-

medication has become a national policy, said Toshiaki

Yoshino, JSMI chairman, Rohto Pharmaceutical.

The proposal to make OTC medicines tax deductable on

annual spends over US$10 would allow people to claim

8

Recent and groundbreaking initiatives which have

been successful in tackling a range of public health

concerns were presented at a session chaired by

June Raine, Chair of the EMA Pharmacovigilance

Risk Assessment Committee (PRAC) and Director of

Vigilance Risk Management of Medicines at

(MHRA).

Antoine Bon, Vice President of the French self-care

industry association, AFIPA, described how the

Association and industry have worked to promote

the responsible use of vasoconstrictors following

concerns over adverse cardiovascular and

neurological effects.

The partners have established an ongoing

epidemiological study, and AFIPA has launched a

Risk Minimisation Plan (RMP), which has been well

received by pharmacists and patients, as well as a

website advising on the proper use of

vasoconstrictors and the use of a QR code on

patient leaflets.

As a result of this approach, no products have been

“back switched,” said Mr Bon, while the confidence

and trust of all stakeholders have been maintained.

The initiative has also led to enhanced disclosure

between the Ministry of Health and the industry,

with the establishment of a joint committee, which

Mr Bon described as “an open door for dialogue

and co-responsibility,” adding that “this will be

continued – this is not a sprint, it is a marathon.”

Scott Melville, president and CEO of the US

Consumer Healthcare Products Association (CHPA),

described an innovative risk mitigation strategy

undertaken by the CHPA after it was discovered

that US teens were abusing the OTC cough

treatment ingredient dextromethorphan (DXM).

The Food and Drug Administration (FDA) was

back 5-20 per cent of the purchase amount, as well

as the possibility of growing the existing OTC mar-

ket by 40 per cent, explained Yoshino.

In Mexico, recent regulatory reforms have made

promoting innovation a priority said Mr Mario

Alanis, Economic Advisor to the Federal Commis-

sioner of COFEPRIS, the Mexican medicines regula-

tory agency.

The removal of hampering regulations, such as the

requirement to have the manufacturing plant in

Mexico, together with streamlining the licensing

process, means that Mexico is now the fastest

country in the world to authorise the marketing of

new molecules, while still meeting internationally

recognised standards of safety, quality

and efficacy.

Building trust

Toshiaki Yoshino, Natalie Gauld

and Mario Alanis Garza

9

Gwenole Cozigou, Director at DG Enterprise and Industry at the European Commission, discussed the

outcomes of the European Commission’s Project Group on Promoting Good Governance for non-

prescription medicines.

He explained the outcomes of the multi-stakeholder platform, noting that there is wide recognition that

medicines’ switches to non-prescription status are beneficial if they: enable quicker access to treatments,

with no waiting times in doctors’ surgeries; expand therapeutic choice, especially for minor ailments; free up

doctors’ time; and save public health funds.

Pointing out the vast differences in EU member states’ cultures, traditions and attitudes in healthcare

related issues, Cozigou urged stakeholders to get behind the process of promoting self-care at the national

level.

Meeting report

EU report on non-prescription medicines

Gwenole Cozigou, Antoine Bon, June Raine, Scott Melville, Antonio Gaudioso

considering making DXM a controlled substance.

However, “our plan was to use evidence-based

interventions to change teen attitudes and

behaviour that lead to the abuse of DXM,” said Mr

Melville. “Our aim was to get teens to think: “I don’t

want to be that guy/girl.”

The key factors of success for this initiative

included the regular “checking in” with regulators

and building trust with data and partnering with

trusted voices, he said.

Antonio Gaudioso, Secretary General of Italy’s

Cittadinanzattiva (Active Citizen) network, detailed

how the group has worked to support student

safety through empowerment and supporting

health education in schools.

He stressed the importance of using peer

education – “training the trainers” - and of a multi-

stakeholder approach. Working together over a

long period, to drive change and build trust is

essential.

10

Consumers today know that they have to take a more

active role in keeping themselves healthy and want to

engage with healthcare professionals about their

health, according to Ilaria Passarani, Head of the Food

and Health Department at the European Consumer

Organisation BEUC. “As a consumer, if you want to

engage with me, you need to know me,” she told

delegates.

Describing what the consumer wants from a non-

prescription medicine, Ms Passarani said: “I want to

know that it will work for me, with few side effects, that

it is as effective as a prescription medicine and that I

can afford it.”

In a session chaired by Matthew Speers, PAGB Chief

Executive, Ms Passarani welcomed the AESGP’s newly-

published guidance for the industry on engaging with

social media, and emphasized the need for companies

to provide consumers with information that is high-

quality. She defined ‘high quality’ information as that

which is: objective and unbiased; consumer-friendly;

evidence-based; up-to-date; accessible; transparent;

relevant and non-promotional. However, she added

that simply providing more information is not enough

without supplying consumers with the right tools to

interpret it or the support of healthcare professionals.

She called for a Europe-wide movement to improve

communication with consumers: “Our national situa-

tions are all very different, but we must work together.”

Engaging with

consumers

Within Europe, pharmacy is the most widely-

distributed resource for health advice; 98 per cent

of EU citizens can reach a pharmacy within 30

minutes and 58 per cent can do so within five

minutes, according to a recent survey by the

Pharmaceutical Group of the European Union

(PGEU).

Customers appreciate pharmacies’ convenient

opening hours, their availability and access and the

fact that they don’t need to make an appointment

for professional advice, PGEU Secretary General

John Chave told the conference. Furthermore, with

current or predicted future shortages of family

doctors in many European countries, and research

showing that as many as 30 per cent of GP visits

may be unnecessary, the opportunities for

pharmacy are growing.

EU patients value pharmacists as a source of self

care advice, and they prefer to collect their

medicines from a pharmacy, even when they are

available from other sources, while national studies

show that pharmacists can detect significant levels

of medication problems through patient

discussions.

Mr Chave highlighted that pharmacists already

perform a vital ‘signposting’ service, acting as the

patient’s first port of call and pointing them to

other healthcare services as needed. They can also

help consumers deal with a range of challenges,

including adhering with their medication regimens

and dealing with unnecessary polypharmacy and

exposure to adverse drug reactions. He added that

these problems are growing and more complex

forms of pharmacy intervention will be needed in

the future to tackle them. “To maintain and

develop this role, we have to ensure that self care

advice fully assures its place as a distinct value-

added service,” said Mr Chave.

Traditional models of pharmacy are changing, and

self-care must be present in the new models,

responding to the changing healthcare

environment and evolving patient needs.

Akira Uehara, John Chave, Ilaria Passarani, Peter Smith, Raj Patel and

Matthew Speers

The role of pharmacy

11

Medical devices and food supplements are

gaining an increasing role in self care, confer-

ence delegates were informed.

Neven Mimica explained the European Com-

mission proposed revisions to the current

framework for medical devices in 2012. Dagmar

Roth-Behrendt provided an overview on the

position of the European Parliament and ad-

dressed the challenges faced in the finalisation

of provisions in order to ensure the appropriate

balance between securing safety and promot-

ing innovation.

Gert Bos, Chair of TEAM-NB, explained the

challenges for notified bodies in getting medi-

cal devices in the market in a timely manner.

Meeting report

Establishing a new

legal framework for

medical devices in

Europe

Gert Bos, Dagmar Roth-Behrendt, Hans Regenauer and Neven Mimica Claudia Heppner, Basil Mathioudakis and Hans Regenauer

Promoting the use of

evidence-supported claims

for food supplements

Claudia Heppner, Head of the Food ingredients and Packaging

Unit at the European Food Safety Authority (EFSA) told delegates

that in the context of food supplements EFSA’s role is to deliver

scientific advice on the safety of food supplements ingredients

(e.g. sources of vitamins and minerals, botanicals but also techno-

logical aids like food colours, sweeteners or preservatives). EFSA

also assesses the scientific justification of the health claims used in

labelling and advertising of food supplements. EFSA engages with

the industry stakeholders, such as the AESGP, to gather relevant

data on ingredients used in food supplements.

Basil Mathioudakis, Head of Nutrition, Food Composition and

Information Unit at the European Commission, explained the

legislative framework and the EU authorisation process for health

claims. Up to date, there are 254 permitted health claims, 1,995

non-authorised health claims and 2,162 health claims still under

consideration, which largely include claims on botanicals. Mr

Mathioudakis also raised an issue of borderline between food

supplements and foods for special medical purposes.

UK health professionals have de-

veloped a number of award-

winning initiatives to support and

communicate national efforts to

combat anti-microbial resistance.

“This is not about no care – this is

about self care in action, using

global messages, engaging doctors

and promoting self-reliance – eve-

ryone’s a winner,” said Dr Peter

Smith, describing the “NICE 2014

Shared Learning Award” winning

campaign.

Community pharmacist Raj Patel

described the ‘Treat Yourself Better

Without Antibiotics’ a campaign

run nationally by PAGB and Phar-

macy Voice last winter. The cam-

paign’s overall objective was to

position the pharmacy as the place

for people to get advice and treat-

ment for cold and flu symptoms,

rather than seeking a GP visit for an

antibiotic. The ‘Treat Yourself Better

Without Antibiotics’ campaign has

shown the importance of all stake-

holders working together.

Self-care initiatives in the UK

12

Societies are ageing, but we want

to be ageing “healthily and beauti-

fully,” said Akira Uehara, chair and

CEO of Taisho Pharmaceutical Co.

In Japan extending healthy life

expectancy is a central part of the

government’s revitalisation plan for

the nation.

The plan’s measures include the

promotion of OTC medicines, as

well as convenient and accessible

screening for conditions like diabe-

tes.

Delegates were informed by Mr

Uehara that in Japan, priorities for

this year at the national self-

medication industry association

(JSMI) include looking for ways to

motivate consumers towards great-

er self care, monitoring the govern-

ment’s revision of a scheme for

priority Rx-to-OTC product switches

and the establishment of a tax

deductible system for non-

prescription medicines.

“We are working in close colla-

boration with the Japanese phar-

macy association,” added Mr

Uehara.

AESGP and WSMI Directors General, Hubertus Cranz

and Gerald Dziekan, examined at the conference some

of the new priorities and challenges facing their organi-

sations.

“We have to adapt to a changing environment which is

bringing more and more stakeholders in. We must

reach out and build new alliances with these new

emerging stakeholders,” explained WSMI Director Gen-

eral Gerald Dziekan. One way to do this is to reach out

to industries in new regions.

For example, the WSMI has recently welcomed Kenya’s

OTC industry association as a member, and is seeking

more engagement not only in Africa but also the Mid-

dle East and parts of Asia.

AESGP Director General Hubertus Cranz explained that

AESGP and WSMI are aligned and target the main chal-

lenges of the sector: Ingredient defense, switches,

branding, advertising, and adequate rules related to

environment and falsification.

Future AESGP and WSMI priorities

Jaume Pey, Hubertus Cranz, Gerald Dziekan and Bélen Crespo

Healthy ageing

The conference was closed by Bélen Crespo, Executive Director of the Agency for Medicines and Health Products

(AEMPS), Spain, and Jaume Pey, Executive Director of anefp, who jointly invited participants to the 51st AESGP

Annual Meeting that will take pace in Barcelona on 26-28 May 2015.

■ Updated EURD list

A revised version of the List of Union reference dates and frequency of periodic safety update reports (‘EURD List’)

was published on 28 May 2014.

Medicines

Pharmacovigilance

■ PRAC April Meeting Minutes

The Minutes of the Pharmacovigi-

lance Risk Assessment Committee

(PRAC) meeting of 7-10 April 2014

were published on 8 May 2014 and

include the following points of

interest:

Review of ambroxol and

bromhexine

The PRAC noted the safety con-

cerns identified by Belgium for

ambroxol-containing products.

Since ambroxol is a major metabo-

lite of bromhexine, the PRAC

agreed that products containing

bromhexine should also be in-

cluded in the review. Finally the

PRAC discussed a list of questions

to be addressed by relevant MAHs

during the procedure as well as a

timetable for conducting the re-

view.

Review of codeine-containing

medicines when used for cough

and cold in children

The PRAC noted the notification

letter from the German Medicines

Agency and discussed a list of

questions to be addressed by rele-

vant MAHs during the procedure as

well as a timetable for conducting

the review. The PRAC requested

interaction and involvement of the

EMA Paediatric Committee (PDCO)

in the review.

Signal of association with cardio-

vascular events from the use of

sodium containing formulations

of effervescent, dispersible and

soluble medicines

The PRAC commented that in the

study the association between

hypertension and soluble medicines

was strong (OR 7.18) supporting a

limited role for confounding. Howe-

ver, it was emphasised that a cohort

study design would have been

more appropriate as the outcomes

examined were relatively common;

there was a lack of adjustments for

duration of treatment in the analy-

sis conducted in a heterogeneous

group of patients, including both

those with intermittent use of the

medicinal products and those with

prolonged use; patients’ dietary

intake was not available and hence

had not been included in the analy-

sis. Despite the limitations of the

study, however, the PRAC con-

curred that it is well established

that high sodium intake (most

commonly as dietary sodium chlo-

ride (salt)), is associated with car-

diovascular events particularly

hypertension and stroke. Therefore

the association seen in the study

between soluble medicines contai-

ning sodium and non-fatal stroke

can be considered plausible.

The PRAC noted that sodium is

listed in the guideline ‘Excipients in

the label and package leaflet of

medicinal products for human use’

and that there are provisions in

place for labelling of sodium con-

taining medicines for oral use

where sodium is > 1mmol* / dose;

reporting: ‘This medicinal product

contains x mmol (or y mg) sodium

per dose. To be taken into conside-

ration by patients on a controlled

sodium diet’. The PRAC debated on

whether this wording could be

further expanded and clarified and

agreed that this should be further

investigated.

Summary of recommendation(s)

The PRAC recommended that there

should be engagement with the

EMA Excipients guideline group to

consider whether updates could be

made to the labelling of sodium

within the 2003 Guideline in order

to make the sodium labelling clea-

rer and more meaningful for pa-

tients. In particular, how the label-

ling can more clearly express so-

dium content in medicines in the

context of ‘dietary salt’. EMA secre-

tariat will work closely with the

PRAC Rapporteur and present a

follow-up to the PRAC, which is

expected in September 2014.

13 AESGP Euro OTC News | Issue 259

On 10 June 2014, the EMA publi-

shed the agenda of the Pharma-

covigilance Risk Assessment Com-

mittee (PRAC) meeting taking place

on 10-13 June 2014. It includes:

Referrals

Start of a Review of the benefit-

risk balance of Ibuprofen (NAP)

following notification by the

United Kingdom of a referral

under Article 31 of Directive

2001/83/EC, based on pharma-

covigilance data (Newly trig-

gered procedures – item 3.1.1.)

A press release published on 13

June 2014 clarified that only

ibuprofen taken at high dose

was linked to cardiovascular

risks and that the PRAC will

consider the data available

relating to high-dose ibuprofen

(2.400 mg/day)

Review of the benefit-risk ba-

lance of Hydroxyzine following

notification by Hungary of a

referral under Article 31 of Di-

rective 2001/83/EC, based on

pharmacovigilance data (item

3.2.2.)

Signals

Signal of risk of chemical

injury including burns from

the use of Chlorhexidine

(NAP) in skin disinfection in

premature infants (New

signals detected from other

sources – Item 4.2.1.)

Signal of haemolytic anaemia

from the use of Lansoprazole

(item 4.3.4.)

Other

Discussion on the draft PRAC

work programme 2014-2015

(item 12.1.1.).

Discussion on a Guidance

document on EudraVigilance

analysis to support commu-

nity procedures (item 12.5.1.)

The outcome of these discussions

may be reported in the meeting

highlights to be published shortly

after the meeting.

■ NtA - Revised Chapter 3 Vol. 2A “Union Referral Procedures”

The European Commission released a revision of chap-

ter 3 “Union Referral Procedures” of Volume 2A of the

Notice to Applicants in May 2014.

The chapter was revised to reflect the modifications

following from the pharmacovigilance legislation, con-

cerning Articles 31 (safety referrals) and 107i (urgent

union procedure). Amongst others, it is interesting to

note that the EC’s interpretation of an article 3 referral

is triggered by an applicant / MAH:

“[…] if the referrer is an applicant/marketing authorisa-

tion holder, in advance of initiating a referral under this

Article, he must contact a Member State or the Commis-

sion with a request to assess and confirm the Union

interest before the matter is referred to the relevant

Committee/EMA.”

Clinical trials

■ EMA policy on CT data transparency getting through despite opposition

Ombudsman concerned about

change of EMA policy on CT data

transparency

The European Commission has

informed, in a letter to the Europe-

an Medicines Agency (EMA), that

the European Ombudsman, Emily

O'Reilly, has expressed concern

about what appears to be a signifi-

cant change of policy concerning

clinical trial data transparency.

According to documents the Om-

budsman has seen, EMA is planning

to limit access to clinical trial data

by imposing strict confidentiality

requirements and by allowing data

only to be seen on screen using an

interface provided by EMA, as well

as imposing wide restrictions on

the use of such data.

Emily O'Reilly commented: “We

were pleased when EMA announced,

in 2012, a new pro-active transpa-

rency policy, giving the broadest

possible public access to clinical trial

data. I am now concerned about

what appears to be a significant

change in EMA's policy, which could

undermine the fundamental right of

public access to documents establis-

hed by EU law. European citizens,

doctors and researchers need maxi-

mum information about the medi-

cines they take, prescribe and ana-

lyse.”

■ PRAC June Meeting Agenda

14 AESGP Euro OTC News | Issue 259

■ EMA policy on CT data agreed by EMA Management Board

On 12 June 2014, the EMA announced that the EMA Management Board agreed on the policy on publication of

clinical trial data, together with more user-friendly amendments proposed by EMA Executive Director Guido Rasi, that

will both allow the Agency to proactively publish clinical trial data that are submitted as part of marketing authorisa-

tion applications, and give the possibility to download, save and print the trial data for academic and non-

commercial research purposes.

Next steps

In light of discussions at the Board, the wording of the policy, including practical arrangements for academic and non

-commercial research users, will now be finalised with a view to its adoption by the Board through written procedure

by mid-July 2014, and will be effective from 1 October 2014. Importantly, the Agency will ensure that the policy will

not prejudice citizens’ rights under existing access to documents legislation and the new clinical trials regulation.

■ CT Regulation published in the OJ

The Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on

medicinal products for human use, and repealing Directive 2001/20/EC was published in the Official Journal (L 158/1)

on 27 May 2014.

This Regulation will enter into force on 16 June 2014.

EMA response: no intention to im-

pede transparency

On 22 May 2014, the Agency pu-

blished its response to Ombuds-

man’s letter of 13 May 2014,

which stresses that the policy is

intended to further increase trans-

parency of clinical trial data, and

that there is no intention to intro-

duce any hurdle to the implemen-

tation of EU legislation on access to

documents. It gives the following

explanations:

“This new transparency measure is

different in both scope and legal

basis from Regulation (EC) No

1049/2001, which is applicable to

EMA documents via Article 73 of

Regulation (EC) No 726/2004.

[…] the new policy will not apply to

clinical study reports submitted to

the EMA prior to its entry into force

(estimated between October 2014

and January 2015), the so-called

'legacy' documents, nor can it apply

to clinical study reports on non-

centrally authorised medicinal pro-

ducts which are outside of EMA's

remit. Of course, for such 'legacy'

documents, Regulation (EC)

1049/2001 will continue to apply.

As to the modalities to which re-

questors will have access to the

documents under the new policy, the

adoption of the 'Terms of Use' and

the 'screen-only-mode' was deemed

a reasonable compromise among

the interests of all stakeholders and

institutions we consulted, having in

mind the Commission's clear mes-

sage that we would also have to

assure compliance with national and

international obligations that all

European institutions have to com-

ply with, including but not limited to

the TRIPS Agreements and copyright

laws.

The new clinical trial regulation will

provide a considerable increase in

transparency of clinical trials con-

ducted in the EU and of their results.

It also recognises the concept of

possible commercial confidentiality

in the context of the EU Database,

whilst confirming that the data

included in clinical study reports is

not in general commercially confi-

dential. This is also the view of the

Agency and is reflected in our new

draft policy.

The new measure will be user-

friendly, allowing the reports to be

continuously available to the public

and searchable so that users can

consult them at will without the

need for a specific request for access

to EMA. Finally, there is no intention

on our side to limit the academics'

freedom to review the data, or refer

to the reports in publications or

communications with colleagues/

peers.

Our new policy will make all the

above mentioned clinical study

reports publicly available in a syste-

matic way. As to the relationship

between this new measure and the

provisions of Regulation (EC) No

1049/2001, this aspect will be consi-

dered within the framework of our

on-going discussions with the Euro-

pean Commission. There is no inten-

tion to introduce any hurdle to the

implementation of Regulation (EC)

No 1049/2001.”

15 AESGP Euro OTC News | Issue 259

Art. 57(2) / XEVMPD

■ EMA Meeting on IT platform arising from new CT regulation

In accordance with the new Clinical Trials Regulation,

the EMA has been given responsibility to develop the IT

platforms that will support sponsors and the experts in

the Member States in carrying out their roles in relation

to the authorisation of trials, their supervision, safety

reporting and compliance activities.

In order to progress the design and development of the

systems including the EU portal and database, the EMA

in collaboration with experts from Member States will

hold a stakeholders meeting on 25 June 2014.

■ Updated XEVMPD controlled vocabularies

The EMA published updated versions of the following

documents relating to Extended EudraVigilance product

report message (XEVMPD) controlled vocabularies:

Extended EudraVigilance product report message

organisations (revision 31)

Extended EudraVigilance product report message

substances (revision 32)

Extended EudraVigilance product report message

pharmaceutical dose forms (revision 10)

Extended EudraVigilance product report message

routes of administration (revision 5)

Cover note on eXtended EudraVigilance Medicinal

Product Dictionary (XEVMPD) substance controlled

vocabulary following the quality control exercise

Pharmacopoeia

■ Report of Annual meeting of National Pharmacopoeia Authorities

On 27 May 2014, the European Directorate for the

Quality of Medicines & HealthCare (EDQM) issued a

press release on the outcomes of the annual meeting of

the National Pharmacopoeia Authorities (NPA) of the 37

Member States of the European Pharmacopoeia which

took place on 7-8 April 2014.

Objective of the meeting

The NPA meeting provides a unique platform for open

and informal exchange of information and discussion

between the secretariats of national pharmacopoeia

authorities and the European Pharmacopoeia and is an

important pillar for the successful collaboration of

Member States in elaborating common and harmonised

standards.

Main discussion items

The implementation strategy for the future ICH Q3D

guideline on Elemental Impurities in the Pharmaco-

poeia, ensuring continued consistency between the

approaches of licensing authorities and the Ph. Eur.

Current quality topics discussed at the European

Medicines Agency’s Joint CHMP/CVMP Quality

Working Party that have a potential impact on the

Ph. Eur., such as the use of co-crystals and other

solid state forms of active substances in medicinal

products and the quality of transdermal patches.

Collaboration between pharmacopoeias and quality

assessors, official medicines control laboratories and

GMP inspectors: NPAs exchanged best practices to

ensure good information-flow between the pharma-

copoeias and regulators responsible for the quality

of medicines and stressed the importance of this

continued collaboration with Health Authorities for

the benefit of patients.

Situation of national pharmacopoeias in member

States: NPAs shared their current practices with

regard to the implementation of the Ph. Eur. in their

respective countries and the situation of the remai-

ning national, country-specific pharmacopoeias.

The next meeting of the National Pharmacopoeia Au-

thorities will take place in the Netherlands in June 2015.

16 AESGP Euro OTC News | Issue 259

CMDh

■ CMDh May Report

The CMDh has recently published

the report from its meeting held on

19-21 May 2014, which includes:

Outcomes of informal PSUR

work-sharing procedures

The CMDh has recently adopted

the conclusions of PSUR as-

sessments for, amongst other subs-

tances, oxybutynin hydrochloride.

Electronic submissions via the

CESP

The CMDh strongly advises appli-

cants submitting their electronic

dossiers via the CESP (Common

European Submission Platform) to

carefully follow the instructions

given in the guidance document

available on the CESP-website when

uploading their applications. In

particular, the CMDh would like to

emphasise the importance of ente-

ring the complete and correctly

formatted procedure number when

preparing the CESP delivery file for

post-authorisation procedures such

as variations and renewals.

Regulation (EC) No 1234/2008 on

variations

The CMDh has agreed on a new

recommendation for the classifica-

tion of an unforeseen variation:

concerning the introduction of Ph.

Eur. 2.9.6 “Uniformity of content of

single-dose preparations” and/or

Ph. Eur. 2.9.5 “Uniformity of mass of

single-dose preparations”, as ap-

propriate, to replace the currently

registered Ph. Eur. 2.9.40

“Uniformity of dosage units (by

CU)” [B.II.d.1.z (control of finished

product)]

Meeting between the CMDh and

Interested Parties

The CMDh met with Interested

Parties in the margin of the May

meeting to discuss proposals for

improvement of MR/DC procedures

and how to best implement the

pharmacovigilance legislation. A

progress report was given to IPs on

the pilot on work-sharing

procedure for the assessment of

Active Substance Master Files.

Presidency CMDh meeting

The CMDh convened for a Presi-

dency meeting on 8th and 9th May

2014 in Bonn, Germany, held as

part of a programme of events

organised under the Greek Presi-

dency of the Council of the EU. The

CMDh discussed, amongst others,

topics related to pharmacovigilance

(safety referrals, RMPs, signal ma-

nagement, PSURs), renewals, the

type II variation timetable and fixed

-dose combinations.

Other

Revised Q&A on Pharmacovigi-

lance Legislation – Updated to

give information on where to

find the outcomes of PSUR

assessments that concern cen-

trally approved products only or

a mix of centrally and nationally

approved products.

Revised mandate for the

working group on CTS

(Communication Tracking Sys-

tem).

Updated information on applica-

tions referred to the CMDh in

accordance with article 29(1) of

Directive 2001/83/EC and Article

13 of Regulation (EC) No

1234/2008.

Updated list of substances for

which data has been submitted

in accordance with Article 45 of

the Paediatric Regulation.

Statistics

20 mutual recognition

procedures started in April 2014,

of which 5 related to non-

prescription medicines in the

reference Member State.

60 decentralised procedures

started during that period, of

which 6 related to non-

prescription medicines in the

reference Member State (see

graph on page 18).

■ Updated list of substances under PSUR Work Sharing Scheme

In May 2014, the CMDh published an update of the list

of substances under PSUR Work Sharing Scheme and

other substances contained in National Authorised

Products with DLP synchronised (Excel / PDF version).

No changes concerning substances in our sector were

detected since the last update.

An Assessment of Periodic Safety Update Reports for

Nationally Authorised Products in 2013/2014 – Cover

Note has also been recently published, which gives

more details on the legal implications, the conse-

quences for removing the substances concerned from

the EURD list and the changes made to the new PSUR

WS list.

17 AESGP Euro OTC News | Issue 259

i

EMA

■ EMA revised Q&A related to pharmacokinetic matters

In the context of assessment procedures, the

Pharmacokinetics Working Party (PKWP), or its

predecessor the Therapeutic Subgroup on

Pharmacokinetics of the Efficacy Working Party (EWP-

PK subgroup), is occasionally consulted by the CHMP

or, following CHMP’s agreement, by other Committees,

Working parties or the CMD(h). The objective is to

address specific questions in relation to

pharmacokinetic evaluations and particularly the

requirements and assessment of bioequivalence

studies. The positions, which are being elaborated by

the PKWP in response to such questions, are being

forwarded to the enquiring party for consideration in

their assessment.

It is understood that such position will be reflected in

the procedure-related assessment reports if applicable.

In some cases however, these position might also be of

more general interest as they interpret a very specific

aspect that would not necessarily be covered by

guidelines. This paper summarises these positions

which have been identified as being within this scope.

In addition, general clarifications related to guidelines

authored by the PKWP are subject to specific positions

in this paper.

The positions in this document are addressing very

specific aspects. They should not be quoted as product-

specific advice on a particular matter as this may

require reflection of specific data available for this

product. By no means should these positions be

understood as being legally enforceable.

A revised version of the “Questions & Answers: Positions on specific questions addressed to the Pharmacokinetics

working party” was published on 2 May 2014.

It includes a new position (No. 19) on ‘Ebastine: use of metabolite data to demonstrate bioequivalence between

inactive pro-drugs’.

■ EMA CHMP May Meeting Highlights

On 23 May 2014, the EMA Committee for Medicinal

Products for Human Use (CHMP) published the

highlights from its meeting held on 19-22 May 2014,

which include the following organisational matters:

The appointment of Barbara van Zwieten Boot as

chair of the EMA Guidelines Consistency Group and

the adoption of an updated mandate for this group.

18 AESGP Euro OTC News | Issue 259

■ EMA Management Board March Meeting Minutes

On 5 May 2014, the EMA published the minutes of the

EMA Management Board meeting of 19-20 March 2014.

In addition to what was reported in AESGP Euro OTC

News 257 on the highlights of the meeting, the follow-

ing may be noted:

Management Board data gathering initiative

The Board decided at the December 2013 meeting to

develop a programme to gather the evidence needed

by the European Commission in drafting the future

legislative proposal on fees. Various elements that

should be considered within the data-gathering exercise

were suggested: Clear definitions of scientific work and

scientific-coordination work are needed; a vision of the

relation between EMA and NCA tasks is necessary; the

exercise should look at both remunerated and non-

remunerated activities; support needed for committees

to make good scientific decisions needs to be de-

scribed; the methodology should be geared to capture

time spent on activities, rather than their financial cost;

membership of the steering group should reflect experi-

ence with centralised activities, but also the complexity

of the system, as different NCAs need different levels of

support; time recording alone cannot convey the totali-

ty of what is being done and which can be termed

'regulatory science'; systems to maintain collected data

sets for the future should be explored.

Review and Reconnect update

The product team leader (PTL) will now be split into two

new roles: a procedure manager (PM) to oversee the

management of specific procedures and act as a prima-

ry contact point, and an EMA product lead (EPL) to

maintain oversight of a medicine through the different

stages of its lifecycle. Roles will be distinguished without

new jobs being created. Both regulatory and legal ad-

vice will be sought at an early stage and throughout the

processes as appropriate. These new processes should

provide benefits for the NCAs as well, as it will allow

them to focus their contribution on high-value work. As

knowledge is transferred through the lifecycle, the

capacity of scientific committees to deliver high-quality

opinions is increased.

Report from the Commission

Preparation of Delegated Act on Post-authorisation

efficacy studies (planned publication Q2 2014).

■ EMA Management Board re-elects Sir Kent Woods as Chair

The EMA has announced that the Management Board, at its meeting on 12 June 2014, re-elected Sir Kent Woods as

its chair for a three-year mandate.

The former Chief Executive of the Medicines and Healthcare products Regulatory Agency (MHRA) of the United

Kingdom is one of the longest-serving members on the EMA Management Board. This is his second and final

mandate, as the rules of procedure of the Board foresee a maximum of two terms.

Information on the revised EMA policy on the

handling of declaration of interests for scientific

committees’ members and experts. The aim of the

revision should enable a better balance at managing

Declaration of Interests (DoIs) versus accessing the

best expertise without dropping standards when

assessing DoIs.

Follow-up discussion on principles to revise the RMP

assessment process.

The adoption of two ICH Questions & Answers

documents:

ICH E2C(R2) Guideline: Periodic Benefit-Risk

Evaluation Report Questions & Answers (CHMP/

ICH/271908/2014)

ICH E14 Guideline: The Clinical Evaluation of QT/QTc

Interval Prolongation and Proarrhythmic Potential for

Non-Antiarrhythmic Drugs Questions & Answers (R2)

(CHMP/ICH/310133/2008)

Initial discussion regarding proposed changes for

processing some type II variations.

Initial discussion regarding the mandate, objectives

and rules of procedures for establishing a new Inter-

Committee ad hoc Ethics Advisory Group.

The minutes of the previous meeting, held on 22-25

April, were also released on 22 May 2014.

19 AESGP Euro OTC News | Issue 259

ECJ

■ Final QP declaration template and accompanying Guidance

On 21 May 2014, the EMA publis-

hed the final QP declaration tem-

plate (Qualified Person’s declara-

tion concerning GMP compliance of

the active substance manufacture).

The AESGP and industry comments

have been taken into account and

the final template is leaner than the

original draft.

The Guidance for the QP declara-

tion template was also published

on 21 May 2014. AESGP is pleased

to note both references to atypical

active (AA) and to the specific EMA

Q&A relative to AA as follows:

“Exceptional circumstances, when an

on-site audit is not practical (e.g.

atypical actives11), are out of scope

of the declaration template.

An off-site, remote or “paper-based”

audit may be justifiable in terms of

benefit risk, but this can only be

considered on a case-by-case basis.

In these cases, a suitable quality

system is expected to be applied by

the active substance and finished

product manufacturers. As a prin-

ciple, such controls must provide

confidence that the active substance

is fit for purpose and will not negati-

vely affect the safety and efficacy of

the medicinal product. The QP is

expected to justify the controls in

place on a scientific basis and record

a risk assessment on a product

specific basis.

Specific guidance addresses the case

of non-traditional (or atypical)

active substances and veterinary

ectoparasiticides.

In these exceptional circumstances,

the QP declaration should be sup-

ported by:

sessment of GMP compliance in lieu

of on-site audit;

forming the basis of the off-site

audit, for example - questionnaires,

review of documents, ISO 9000

certification, results of analytical

testing and historical experience

with the supplier, and risk analysis.”

■ Final QP declaration template and Guidance

The Advocate-General of the Euro-

pean Court of Justice delivered an

opinion on a case brought by a

Latvian company (Olainfarm)

against the Latvian Ministry of

Health (Case C-104/13) on 20 May

2014.

Questions referred

On a proper construction of Article

10 or of any other provision of Di-

rective 2001/83/EC of the European

Parliament and of the Council of 6

November 2001 on the Community

code relating to medicinal products

for human use, has the manufactu-

rer of a reference medicinal product

an individual right to bring an ac-

tion challenging the decision of a

competent authority by which a

generic medicinal product of ano-

Procedural aspects of fees for pharmacovigilance

(planned applicability Q3 2014 for procedure-based fees

and 1 July 2015 for annual fee).

Preliminary draft work programme 2015

The Agency intends to respond to these challenges

(high cost of R&D globalisation) by supporting early

stages of medicines development through a 'one-stop

shop' approach, facilitating provision of scientific advice,

which has proven to have a positive effect on the out-

come of marketing-authorisation applications and the

availability of medicines to patients.

The Agency intends to continue to focus on internation-

al collaboration among regulators, particularly in the

field of inspections, and on openness and patient en-

gagement, with its efforts concerning access to clinical-

trial data. The Agency must further continue to manage

increasing tasks stemming from new legislation, effec-

tively managing complexity and constant growth in

workload. Focus remains on delivering high-quality

assessment activities and contributing towards building

a strong network. This is dependent on NCAs being

strong, healthy and adequately funded. The Agency

intends to further develop its collaboration with the

NCAs by developing IT systems that deliver benefit to

the network through joint allocation of telematics funds,

support to training initiatives, increased exchange of

experts, and support to the multinational-assessment-

teams initiative, facilitating participation of smaller

NCAs in the centralised activities.

20 AESGP Euro OTC News | Issue 259

■ ECJ Cases C-358/13 & C-181/14 - Definition of medicinal product

The Advocate-General of the Euro-

pean Court of Justice (ECJ) issued

an opinion on 12 June on the follo-

wing questions referred by the

Bundesgerichtshof (German Federal

Court of Justice) to the ECJ:

Can an association of aromatic

herbs and synthetic cannabi-

noids, aimed at provoking effects

similar to those of cannabis, be

considered a medicinal product in

the sense of Article 1(2)(b) of Direc-

tive 2001/83/EC as amended?

In other words, is the definition

of ‘medicinal product’ liable to

cover a substance or a composition

capable of modifying the physiolo-

gical functions in human beings but

whose intake is only aimed at pure-

ly recreational purposes, and not at

preventing or treating a disease?

The Advocate General concluded

that the notion of ‘medicinal pro-

duct’ as defined in Article 1(2)(b) of

Directive 2001/83/EC as amended

must be interpreted in the sense

that it does not apply to a subs-

tance or association thereof, such

as that of aromatic herbs and

synthetic cannabinoids, capable of

modifying the physiological func-

tions in human beings but whose

intake is only aimed at purely re-

creational purposes, and not at

preventing or treating a disease.

Further information on the case

may be found at the following link:

http://goo.gl/ck5WaL (not yet

available in English).

Guidelines for comments

■ AESGP comments on Q&As

Further to the information released in AESGP Euro OTC News 256, and based on the input received, AESGP sent

comments on:

the Q&As on Benzyl alcohol

the Q&As on Ethanol

in the context of the revision of the guideline on ‘excipients in the label and package leaflet of medicinal products for

human use’.

ther manufacturer of medicinal

products was registered, using as the

reference medicinal product the

product registered by the manufac-

turer of the reference medicinal

product? In other words, does that

Directive confer on the manufactu-

rer of the reference medicinal pro-

duct the right to a judicial remedy,

the object of which is to determine

whether the manufacturer of the

generic medicinal product made

lawful, well-founded reference to the

product registered by the manufac-

turer of the reference medicinal

product, relying on Article 10 of the

Directive?

If the reply to the first question

should be affirmative, on a proper

construction of Articles 10 and 10a

of the Directive, may a medicinal

product registered in accordance

with Article 10a of the Directive as a

medicinal product in well-

established medicinal use be used as

a reference medicinal product for

the purpose of Article 10(2)(a)?

Conclusions of the Advocate-

General

A medicinal product registered in

accordance with Article 10a of Di-

rective 2001/83/EC of the European

Parliament and of the Council of

6 November 2001 on the Communi-

ty code relating to medicinal pro-

ducts for human use, as amended by

Directive 2004/27/EC of 31 March

2004, may be employed as a refe-

rence medicinal product for the

purposes of Article 10(2)(a) of the

directive.

Article 10(1) of Directive 2001/83

must be interpreted as conferring on

the holder of a marketing authorisa-

tion for a reference medicinal pro-

duct the right to challenge the mar-

keting authorisation for a generic

which uses that medicinal product

as the reference product during the

ten-year protection period (or, as the

case may be, eleven-year period) to

which the holder is entitled under

that directive.

Further information on the case

may be found at the following link:

http://goo.gl/RhQPIL. The final

judgment of the European Court of

Justice will follow.

21 AESGP Euro OTC News | Issue 259

Following consumption of dextro-

methorphan cough syrups

contaminated with levome-

thorphan approximately 50

persons died in Pakistan in

January 2013. A further suspected

drug intoxication involving 11

patients was reported several

months later, in September 2013,

in Paraguay. Investigations

revealed that the medicines

administered were manufactured

using adulterated dextrome-

thorphan hydrobromide, which

contained levomethorphan at

levels varying between 9.5% to

22.6%. Following these incidents

the World Health Organization

issued Drug Alerts No 126 and

129 and called on all Member

States to increase vigilance

against adulterated Dextrome-

thorphan/Dextromethorphan

hydrobromide API.

It is proposed to revise the

monograph on Dextrome-

thorphan hydrobromide in The

International Pharmacopoeia with

a view to add a statement under

the section “Manufacture” requir-

ing that the production method is

validated to demonstrate that the

substance, if tested, would

comply with a limit of not more

than 0.1% for levomethorphan

hydrobromide. This limit was

deemed appropriate following a

scientific assessment on behalf of

the WHO Prequalification Team. A

chiral method, selective for

levomethorphan, is currently

under development and shall be

included in the “Supplementary

Information Section” of The

International Pharmacopoeia

once elaborated.

i

■ Draft detailed guide on monitoring of medical literature

The EMA released for comments the Draft detailed

guide regarding the monitoring of medical literature

and the entry of relevant information into the Eudra-

Vigilance database by the EMA on 26 May 2014.

This detailed guide describes the technical aspects of

the literature-monitoring services to be provided by the

Agency in line with the requirements set out in Article

27 of Regulation (EC) 726/2004 and GVP module VI.

Key principles raised by the pharmaceutical industry

Alleviate the burden on maximum number of MAHs.

Innovative medicinal products should not be co-

vered.

Avoid partial service that would necessitate duplica-

tive efforts by MAHs.

Provide quality controlled literature-monitoring

services.

Establish a process so that MAHs can comply with

the worldwide regulatory requirements.

Members are asked to send their comments on this

document by 11 July 2014.

■ ICH Q7 Q&A for comments

The ICH Q7 Q&A has now been

released for comments by the

Steering Committee (SC) at its last

meeting in Minneapolis.

The Q7 Implementation Working

Group (IWG) was endorsed by the

ICH Steering Committee in October

2012 to elaborate a Q&A on Q7

aiming at clarifying interpretation

of some sections.

In addition, technical issues with

regard to GMP of APIs, also in the

context of new ICH guidelines, were

addressed in order to harmonise

expectations during inspections

and to remove ambiguities and

uncertainties.

Next steps

The Q&A is intended to be finalised

at the next ICH meeting in Lisbon

on 8-13 November 2014.

Members are asked to send their

comments on the draft ICH Q7

Q&A by 22 August 2014.

22 AESGP Euro OTC News | Issue 259

■ WHO Draft monographs on Pyrantel

The WHO draft monographs for future publication in the International Pharmacopeia is for comments until 11 July

2014. Comments will be sent back to WSMI.

pyrantel chewable tablets (QAS/14.587)

pyrantel tablets (QAS/14.588)

pyrantel embonate (QAS/14.589)

■ WHO Storage and Transport Technical Supplements

The WHO Model Guidance for the storage and transport

of time- and temperature- sensitive pharmaceutical

products was developed in consultation with the ‘WHO

Task Force on Regulatory Oversight on Pharmaceutical

Cold Chain Management’ and was publis-

hed in 2011 as Annex 9 to the 45th

report of the

Expert Committee on Specifications for Pharmaceutical

Preparations (see page 324 of WHO Technical Report

Series N° 961, 2011). It was decided at the WHO Expert

Committee on Specifications for Pharmaceutical Prepa-

rations in October 2013 that 18 supplements to the

Model Guidance would be circulated through the WHO

usual consultation process for comment.

Herbal news

■ EMA HMPC May Report

On 22 May 2014, the EMA publis-

hed the Report from the Commit-

tee on Herbal Medicinal Products

(HMPC) meeting held on 5-6 May

2014. It includes the following:

Final Community herbal mono-

graphs adopted by the HMPC

Community herbal monograph

on Arnicae flos – adopted by

consensus

Community herbal monograph

on Fucus vesiculosus – adopted

by a majority vote

Revised Community herbal mo-

nograph adopted as a result of

the 5-year systematic review

Community herbal monograph

on Lupuli flos – adopted by a

majority vote

Given the minor changes, a

public consultation was not

deemed necessary by the HMPC.

Draft Community herbal mono-

graph adopted by the HMPC for

public consultation

Draft Community herbal mono-

graph on Agrimonia herba (cf.

our email of 26 May 2014)

Draft Community herbal mono-

graph on Lichen islandicus (cf.

our email of 20 May 2014

Public statement

The HMPC adopted a ‘Public state-

ment on herbal substances contai-

ning constituents associated with

safety concerns’, listing non-

exhaustively some herbal subs-

tances that have been proposed

but are currently not considered a

priority for detailed assessments

because it is foreseeable that a

Community herbal monograph

cannot be established.

Working Party on Community

Monographs and Community List

(MLWP) – Report from the March

2014 Meeting

Revisions

The MLWP continued its work

towards the revision of the mono-

graph (and supporting documents)

on Echinaceae purpureae herba.

Finalisation

No comments have been received

during the public consultation on

the draft monographs on Sisymbrii

23 AESGP Euro OTC News | Issue 259

■ Final CM on Ginseng radix

The EMA HMPC published the final

Community herbal monograph on

Panax ginseng C.A.Meyer, radix

which was adopted by a majority

vote at their meeting on 25 March

2014.

Among the changes made

compared to the draft version

circulated for comments on 17 April

2013, the following may be noted:

Qualitative and quantitative

composition

For preparation D) Dry extract:

‘DERgenuine’ is replaced by ‘DER’ >

‘Dry extract (DER 3-7:1)…’ (also

under section 4.2).

Pharmaceutical form

Preparations B, C and E have been

moved from the 2nd

sentence to the

4th

sentence as they are available

both in liquid and solid dosage

forms (not only in solid dosage

forms). [This reflects the comments

AESGP submitted on 19 July 2013]

4.2 Posology and method of

administration

For preparation D), the following

has been added (underlined): “Dry

extyract (DER 3-7:1), extraction

solvent ethanol 40% V/V, containing

4% ginsenosides (sum of Rb1, Rb2,

Rc, Rd, Re, Rf, Rg1, Rg2)” [partly

reflecting our comments]

The final Community herbal

monograph is available on the

‘Panax’ page, under the ‘All

documents’ tab, together with the

following supporting documents:

Final Assessment Report

Final List of references

Overview of comments received

■ Draft CM Agrimoniae herba

The EMA HMPC published for comments the draft Community herbal monograph on Agrimonia eupatoria L., herba

on 6 May 2014.

The draft assessment report and draft list of references supporting the assessment of Agrimoniae herba have also

been published.

Members are asked to send their comments on this draft monograph (and assessment report) by 1 August 2014.

officinalis herba and Rosae flos. The

documents will be finalised by the

Rapporteurs and transmitted, after

peer-review, to the HMPC for pos-

sible final adoption at the July 2014

meeting.

Drafts

The MLWP endorsed the mono-

graphs on Pilosellae herba cum flore

(re-discussed upon request by the

HMPC) and Eschscholziae herba

cum flore for early peer-review and

transmission to the HMPC for pos-

sible release in July 2014 for public

consultation.

The MLWP further agreed on a

draft public statement on Pi-

crorhizae kurroae rhizoma to stimu-

late submission of data that may

allow further assessment towards a

monograph.

The MLWP also continued its as-

sessment of Carvi aetheroleum,

Carvi fructus, Crataegi folium cum

flore, Myrtilli fructus, Pruni afria-

canae cortex, Sabalis serrulatae

fructus and Silybi marianae fructus.

A first presentation/discussion took

place for Uncariae tomentosae

cortex.

Hearing with AESGP

It is reported that “the MLWP held a

hearing with representatives from

AESGP on 6 May. AESGP welcomed

the further improved transparency

via publication of agendas and

minutes as very useful for industry.

Several topics related to the esta-

blishment of Community herbal

monographs including the extent of

information given in some sections

of traditional use monographs or the

revision procedure. Furthermore

ongoing issues as regards data

availability (use in paediatric popu-

lation, genotoxicity) were discussed

as well as topics potentially related

to the use of Community mono-

graphs and HMPC assessments such

as information on MRP/DCP

procedures for herbal products in the

EU, developments in the food sector

regarding health claims for food

supplements, and tasks performed

by the Agency for herbal substances

in accordance with the pharmacovi-

gilance legislation.”

24 AESGP Euro OTC News | Issue 259

■ Final CM on Ononidis radix

The EMA HMPC published the final

Community herbal monograph on

Ononis spinosa L., radix. which was

adopted by consensus at their

meeting on 25 March 2014.

No changes were made compared

to the draft version circulated for

comments on 20 August 2013.

The final Community herbal

monograph is available on the

‘Ononis’ page, under the ‘All

documents’ tab, together with the

following supporting documents:

Opinion of the HMPC

Final Assessment Report

Final List of references

Overview of comments

■ Rev. CM on Thymi herba

The EMA published the final

revision of the Community herbal

monograph on Thymus vulgaris L.

and Thymus zygis L., herba, which

was modified following the 5-year

systematic review process.

As mentioned in the HMPC report

after the November 2013 meeting,

during which this final version was

adopted by consensus, “given the

minor changes to the monographs, a

public consultation was not

considered necessary after careful

assessment of new scientific data”.

The changes, compared to the

previous version circulated on 26

November 2007, were made in the

following sections:

2. Qualitative and quantitative

composition

The previous text under i) Herbal

substance (“Whole leaves and

flowers separated from the

previously dried stems”) was

replaced by “Not applicable”.

4.1. Therapeutic indications

The text now reads: “Traditional

herbal medicinal product used as an

expectorant in productive cough

associated with cold.”

4.2. Posology and method of

administration

Single and daily doses now

appear together for each

preparation. The daily dose is

now given as an amount of

times daily instead of quantity,

except for preparation c) where

a maximum daily dose of 14 g is

also specified.

For the tinctures, the initial

single and daily doses now apply

to preparation d) Tincture (1:10).

For preparation e) Tincture (1:5),

the following are given: “Single

dose 2-6 ml, 3 times daily”

4.6. Fertility, pregnancy and

lactation

It has been added that no fertility

data are available.

4.8. Undesirable effects

The text now reads:

“Hypersensitivity reactions

(including one case of anaphylactic

shock and one case of Quincke

edema) and stomach disorders have

been observed. Gastric disorders

may occur. The frequency is not

known. If other adverse reactions not

mentioned above occur, a doctor or

a qualified health care practitioner

should be consulted.”

The revised monograph on Thymi

herba, together with the revised

assessment report, opinion of the

HMPC and list of references, are

available on the ‘Thymus’ page,

under the ‘All documents tab’.

■ Final PS on Andrographidis paniculatae folium

The EMA HMPC published the Final Public Statement on

Andrographis paniculata Nees, folium which was

adopted by the HMPC at their meeting on 17

September 2013.

No major changes were made compared to the draft

version circulated for comments on 25 January 2013.

The conclusion remains that a Community herbal

monograph on Andrographis paniculata Nees, folium

cannot be established at present.

The final Public Statement, together with the final

Assessment Report and the final List of references, is

available on the ‘Andrographis’ page, under the ‘All

documents’ tab.

25 AESGP Euro OTC News | Issue 259

CATEGORISATION OF HERBAL PRODUCTS

Panel discussion chaired by: Michèle RIVASI, Member of the European Parliament

· Vittorio SILANO, Medical School, II University of Rome, Italy

· Robert ANTON, Professor Emeritus, Faculty of Pharmacy, University of Strasbourg, France

· Joris GEELEN, Federal Public Service, Health, Food Chain Safety and Environment, Belgium

· Werner KNÖSS, Chair, Committee on Herbal Medicinal Products (HMPC), EMA

· Ioanna CHINOU, Chair, Working Party on Community Monographs and Community List (MLWP), EMA

ENSURING THE RIGHT ASSESSMENT OF FOOD SUPPLEMENTS AND HEALTH CLAIMS

Chair: Pilar AYUSO, Member of the European Parliament

· Valeriu CURTUI, Head of the Nutrition Unit, EFSA

· Amire MAHMOOD, Federal Ministry of Health, Austria

· Basil MATHIOUDAKIS, Head of Unit Nutrition, food composition and information, European Commission

ADJUSTING THE MEDICAL DEVICE LEGISLATION TO CONSUMER NEEDS

Panel discussion chaired by: Mairead McGUINNESS, Member of the European Parliament

· Juozas GALDIKAS, Director, State Health Care Accreditation Agency (VASPVT), Lithuania

· Judite NEVES, Director, Health Products Directorate, Infarmed, Portugal

· Danielle VAN MULUKOM, Ministry of Health, The Netherlands

· Nicola BEDLINGTON, Executive Director, European Patient Forum

· George JESSEN, Member of the AESGP Committee on Medical Devices

CONCLUSION

· Hubertus Cranz, Director General, AESGP

FINDING THE RIGHT BALANCE FOR HERBAL (MEDICINAL) PRODUCTS, FOOD SUPPLEMENTS

AND SELF-CARE MEDICAL DEVICES

Chair: Julie GIRLING, Member of the European Parliament

· Paola TESTORI COGGI, Director General, DG SANCO, European Commission

· Andreas HENSEL, Professor, Institute for Pharmaceutical Biology and Phytochemistry,

University of Münster, Germany

· Ilaria PASSARANI, Head of the Food and Health Department, European Consumer Organisation (BEUC)

Wednesday, 8 October 2014

RECEPTION IN THE EUROPEAN PARLIAMENT’S SALON DES MEMBRES

Welcome by Markus FERBER, Member of the European Parliament

RENAISSANCE HOTEL 19, rue du Parnasse, Brussels

Tuesday, 7 October 2014

Herbal (medicinal) products, food supplements, self-care medical devices

Paving the way towards a coherent system

Brussels, 7-8 October 2014 | aesgp.eu/BRU

Conference

Food

Food Supplements

■ Commission regulation on methods of sampling of food supplements for citrinin published in the OJ

The Commission Regulation (EU) No 519/2014

amending Regulation (EC) No 401/2006 as regards

methods of sampling of large lots, spices and food

supplements, performance criteria for T-2, HT-2 toxin

and citrinin and screening methods of analysis was

published in the Official Journal of the European Union.

A method of sampling applicable to the official control

of the maximum level established for citrinin in food

supplements based on rice fermented with red yeast

Monascus purpureus is listed in Annex I, point M, and

performance criteria for citrinin are listed in Annex II,

point (h) of this Regulation.

This Regulation will apply from 1 July 2014.

EFSA

■ AESGP participates in EFSA Stakeholder Consultative Platform meeting

On 4-5 June 2014 AESGP participated in the 25th

meeting of EFSA Stakeholder Consultative Platform in

Brussels.

Topics discussed

Among various topics, EFSA discussed with its official

stakeholders some issues of relevance for the food

supplements manufacturers, including:

a feasibility project for introducing electronic

submission of applications at EFSA;

a need for an increased interaction with the

applicants, as well as the current revision of EFSA

Transparency policy with a focus of Conflict of

Interest policy.

Stakeholders consultation

In the context of the e-submission project, the AESGP

highlighted the need to consult the stakeholders at an

early stage of project development in order to take into

account the stakeholders’ input and experience on e-

submissions. Following the AESGP request, EFSA

announced that a public consultation with the

stakeholders will be launched in early 2015.

Interaction with the applicants

EFSA also announced that EFSA recognises a need for a

closer interaction and that more advice should be given

to the applicants, therefore the services to the

applicants will be further developed. Although the

concept of the pre-submission meetings is at the

moment considered difficult to introduce, EFSA

considers other ways of interaction with the applicants

(e.g. trainings or webinars).

Conflict of Interest policy

Regarding the Conflict of Interest policy at the EFSA, the

industry stakeholders, including AESGP, prepared a joint

statement saying that the current EFSA rules are

sufficiently robust to demonstrate the independence of

EFSA experts and EFSA staff. It was highlighted that the

highest standards of scientific expertise of the experts

should be a priority for EFSA in order to maintain the

scientific excellence. Some concerns were expressed

that many high level experts are excluded from

providing input into the EFSA scientific process due to a

perceived conflict of interest.

27 AESGP Euro OTC News | Issue 259

Health claims

■ EFSA opinions on health claims

Article 13(5) claims

On 19 May 2014, EFSA published a

Response to comments on the

Scientific Opinion of the EFSA Panel

on Dietetic Products, Nutrition and

Allergies (NDA) on the scientific

substantiation of health claims

re la ted to cyt id ine 5 ' -

diphosphocholine and maintenance

of normal vision.

Comments originated from the

applicant and were related to the

claimed effect and outcome

measures, the target population,

study population, and extrapolation

from the study population to the

target population.

EFSA has reviewed and shared

these comments with the chair of

the NDA Panel and the chair of the

NDA Working Group on Claims.

In its Opinion published in February

2014 (see AESGP Euro OTC News

256), the NDA Panel concluded that

a cause and effect relationship has

not been established between the

consumption of CDP-choline and

maintenance of normal vision.

The comments received do not

require any change to the

conclusions of the NDA Panel.

Article 14.1(a) claims

On 20 May 2014, EFSA published a

Response to comments on the

Scientific Opinion of the EFSA Panel

on Dietetic Products, Nutrition and

Allergies (NDA) on the modification

of the authorisation of a health

claim related to plant sterol esters

and lowering blood LDL-

cholesterol; high blood LDL-

cholesterol is a risk factor in the

development of (coronary) heart

disease.

Comments originated from the

applicant and were related to the

scientific evaluation of the Panel on

the extension of the conditions of

use to plant sterol esters in powder.

EFSA has reviewed and shared

these comments with the chair of

the NDA Panel and the chair of the

NDA Working Group on Claims.

In its Opinion published in February

2014 (see AESGP Euro OTC News

256), the Panel concluded that

while plant sterols added to foods

such as margarine-type spreads,

mayonnaise, salad dressings, and

dairy products such as milk,

yoghurts, including low-fat

yoghurts, and cheese have been

shown consistently to lower blood

LDL-cholesterol concentrations in a

large number of studies, the

effective dose of plant sterols (as

powder diluted in water) needed to

achieve a given magnitude of effect

in a given timeframe cannot be

established with the data provided.

The study the applicant refers to in

the written comments (and not

submitted in the original

application) does not provide

additional information for the

scientific substantiation of the

extension of the conditions of use

to plant sterol esters in powder.

In the response to comments EFSA

also states that it is the

responsibility of the applicant to

provide the totality of the available

scientific data.

The comments received do not

require any change to the

conclusions of the NDA Panel.

■ Public consultation on EFSA draft Guidance on Statistical Reporting

On 28 May 2014, EFSA launched a public consultation

on a draft Guidance on Statistical Reporting.

The risk assessment process often requires quantitative

evaluation of scientific studies from different sources

(e.g. dossiers, journal publications, technical reports).

The reporting of statistical methodology (including

design), analysis and results varies considerably.

Lack of relevant information can lead to delays in the

review process whilst additional information is sought

from the originating source.

On 20 November 2013, AESGP attended a technical

meeting on the reporting of human studies submitted

for the scientific substantiation of health claims where a

need for a harmonised and standardised way of the

statistical reporting was raised.

In order to assist in the reporting of statistical analysis

and to allow reproducibility of results and to facilitate

independent peer review, the EFSA Assessment and

Methodological Support Unit prepared a draft Guidance

on Statistical Reporting.

The Guidance was prepared to be used by EFSA panels,

Scientific Committee, working groups, units as well as

EFSA applicants.

28 AESGP Euro OTC News | Issue 259

Food additives

■ EFSA statement on a conceptual framework for food additives re-evaluation

Stakeholders submitting statistical analyses to EFSA (e.g.

statistical reports for studies supporting an application)

should also follow these guidelines.

To facilitate the practical use of the guidance, a

template is proposed that covers the reporting of

relevant aspects of a statistical analysis including:

objectives, sources of information (data), study design,

data quality, analysis methods, results and

interpretation.

The document is not intended to provide guidance on

which statistical methodology should be applied and

how statistical analysis should be performed.

Written comments on a draft Guidance on Statistical

Reporting can be submitted to EFSA by 23 July 2014.

Members are asked to send their comments to AESGP

by 8 July 2014.

On 5 June 2014, the EFSA ANS

Panel published a Statement on a

conceptual framework for the risk

assessment of certain food

additives re-evaluated under

Commission Regulation (EU) No

257/2010.

The EFSA ANS Panel was asked to

provide a scientific statement on a

conceptual framework for the risk

assessment of certain food

additives re-evaluated under

Commission Regulation (EU) No

257/2010.

In the context of this re-evaluation,

there are several scientific issues

with the risk assessment of food

additives of low intrinsic toxicity,

e.g. substances with acceptable

daily intake (ADI) “not

specified” (no numerical ADI), food

additives authorised in food

categories according to quantum

satis (QS) and food additives of low

toxicological concern as used in

food.

The ANS Panel stated that it is

frequently confronted by a lack of

usage and analytical data and

toxicity data. In the framework of

the re-evaluation programme, EFSA

has issued public calls for data on

all food additives to be re-

evaluated. In many cases, these

calls for data are unsuccessful,

leaving the ANS Panel in the

position that the safety of the

compound is assessed with limited

and/or inadequate information on

use levels and biological data.

Exposure assessment is an integral

part of the risk assessment and its

absence prevents the ANS Panel

from concluding on the safety of

the food additive concerned.

For those food additives for which

no maximum permitted levels

(MPLs) are set and which are

authorised at QS, information on

actual use levels is required.

In the absence of reliable data,

exposure cannot be estimated.

The document presents exposure

assessment scenarios to be carried

out by the ANS Panel considering

the use levels set in the legislation

and the availability of adequate

usage or analytical data.

The proposed framework will be

used in the evaluation made by the

ANS Panel however a case-by-case

expert judgement remains essential

to reach a final conclusion.

■ EFSA statement on an exposure assessment of Brown HT (E 155)

On 28 May 2014, the EFSA ANS

Panel published a Statement on a

refined exposure assessment of

Brown HT (E 155).

Brown HT (E 155) is a synthetic bis-

azo dye authorised as a food colour

in a number of food categories,

according to Regulation (EC) No

1333/2008 on food additives, inclu-

ding the use in food supplements

at the maximum permitted levels

(MPLs) ranging from 100 to 300

mg/kg.

In 2010, the ANS Panel adopted a

scientific opinion on the re-

evaluation of Brown HT and con-

cluded that dietary exposure in

both adults and 1-10 year old chil-

dren at the high level may exceed

the Acceptable Daily Intake (ADI)

for Brown HT of 1.5 mg/kg body

weight (bw)/day at the upper end

of the range.

Following this conclusion, the Euro-

pean Commission requested EFSA

to perform a refined exposure

assessment for this food colour.

Data on the presence of Brown HT

in foods were requested from rele-

vant stakeholders through a call for

usage and concentration data.

Usage levels were provided to EFSA

29 AESGP Euro OTC News | Issue 259

for six out of 37 food categories in

which Brown HT is authorised. A

limited number of analytical results

were also reported to EFSA.

Exposure assessment was per-

formed using the EFSA Comprehen-

sive Food Consumption Database.

Three different scenarios were

considered, including:

1. exposure estimates based on

Maximum Permitted Levels

(MPLs)

2. a combination of MPLs and

reported maximum use levels

3. reported maximum use levels

only

In the statement, the ANS Panel

concluded that the current expo-

sure estimates of Brown HT (E 155)

provide an update of the exposure

assessment performed in 2010:

First scenario (using MPLs for

calculations) and second scena-

rio (based on the combination of

MPLs and reported maximum

usage levels):

Mean exposure estimates are

above the ADI for toddlers and

children (an almost two-fold

exceedance of the ADI is ob-

served for toddlers).

High level exposure estimates

are above the ADI for all popula-

tion groups (up to four times

higher), with the exception for

the elderly.

Third scenario (based on re-

ported use levels only):

Assuming that Brown HT is not

used in a wide range of food

categories for which the industry

did not provide information, the

mean and high level exposure

estimates of Brown HT are below

the ADI for all population

groups.

Food labelling

■ Directive on labelling honey published in the OJ

The Directive 2014/63/EU amend-

ing Council Directive 2001/110/EC

relating to honey was published on

3 June 2014 in the Official Journal

of the European Union.

The Directive states that pollen,

being a natural constituent particu-

lar to honey, shall not be consi-

dered an ingredient (within the

meaning of point (f) of Article 2(2)

of Regulation (EU) No 1169/2011

on the provision of food informa-

tion to consumers),

The Directive foresees the following

transitional measures: products

placed on the market or labelled

before 24 June 2015, in accordance

with Directive 2001/110/EC, may

continue to be marketed until the

exhaustion of stocks.

This Directive shall enter into force

on the twentieth day following that

of its publication in the Official

Journal of the European Union.

■ Public consultation on EFSA draft Scientific Opinion on the evaluation of allergenic foods and food

ingredients for labelling purposes

On 20 May 2014, the EFSA NDA

Panel launched an open consulta-

tion on the draft scientific opinion

on the evaluation of allergenic

foods and food ingredients for

labelling purposes.

This document updates previous

EFSA opinions relative to food

ingredients or substances with

known allergenic potential listed in

Annex IIIa of 2003/89/EC, as

amended.

These include cereals containing

gluten, milk and dairy products,

eggs, nuts, peanuts, soy, fish, crus-

taceans, molluscs, celery, lupin,

sesame, mustard and sul-

phites.

The Opinion relates to IgE- and non

IgE mediated food allergy, to coe-

liac disease, and to adverse reac-

tions to sulphites in food, and does

not address non-immune mediated

adverse reactions to food. It in-

cludes information on the preva-

lence of food allergy in unselected

populations, on proteins identified

as food allergens, on cross-

reactivities, on the effects of food

processing on allergenicity of foods

and ingredients, on methods for

the detection of allergens and

allergenic foods, on doses observed

to trigger adverse reactions in

sensitive individuals, and on the

approaches which have been used

to derive individual and population

thresholds for selected allergenic

foods.

Written comments might be sub-

mitted to EFSA by 8 August 2014.

AESGP members should send their

comments to this draft opinion on

allergenic foods and food ingre-

dients by 18 July 2014.

30 AESGP Euro OTC News | Issue 259

Medical devices

■ New titles and references of harmonised standards

The updated list of titles and refer-

ences of harmonised standards

under Directive 93/42/EEC was

published in the Official Journal of

the European Union (C 149 of 16

May 2014).

A harmonised standard is a Europe-

an standard elaborated on the basis

of a request from the European

Commission to a recognised Euro-

pean Standards Organisation to

develop compliance with a legal

provision.

In the case of medical devices,

compliance with harmonised stand-

ards provides a presumption of

conformity with the essential re-

quirements of Medical Devices

Directives.

■ Revision of the harmonized standard ISO 14155:2011

The International Standard EN

ISO 14155:2011 “Clinical inves-

tigation of medical devices for

human subjects – Good clini-

cal practice” is currently being

revised at EU level. In this

context, members of the

AESGP Medical Devices Com-

mittee have been invited to

provide comments on the

2011 version of the harmo-

nised standard by 28 July

2014.

■ Council of the EU’s discussions on the proposed regulation on medical devices

The Council of the European Union published further documents on the discussions within the Working Party on

pharmaceuticals and medical devices, notably on the Presidency proposal for Chapter I. This document is of interest

as it gives background information on the outcome reached at the 16 April meeting (see AESGP OTC News 257) i.e

the request of the United Kingdom to re-draft point (h) of Article 1(2) Scope in Chapter I.

■ European Commission’s Expert Groups and Working Groups

AESGP invited to next Vigilance

Medical Devices Expert Group

The next meeting of the Vigilance

Medical Devices Expert Group,

taking place on Friday 11 July 2014,

will be the occasion to discuss the

latest developments regarding the

non-compliance of medical devices.

Working Group on Clinical Investi-

gation and Evaluation

AESGP attended the meeting of the

Working Group on Clinical Investi-

gation and Evaluation (CIE) on 23

May 2014. The Group discussed the

revision of the clinical MEDDEV

(MEDical DEVices) guidance docu-

ments: MEDDEV 2.7/1 ‘Clinical

Evaluation: A Guide for Manufactur-

ers and Notified Bodies’, MEDDEV

2.7/2 ‘Guide for Competent Author-

ities in making assessment of clini-

cal investigation notification’ and

MEDDEV 2.7/3 ‘Clinical Investiga-

tions: Serious Adverse Reporting’. In

addition, AESGP attended the

meeting of the taskforce for the

MEDDEV 2.7/1 on 22 May 2014.

This guidance document together

with MEDDEVs 2.7/2 and 2.7/3 are

expected to be adopted by the

working group at the next meeting

on 27 November 2014.

31 AESGP Euro OTC News | Issue 259

i

ISO 14155:2011 addresses good

clinical practice for the design, con-

duct, recording and reporting of

clinical investigations carried out in

human subjects to assess the safety

or performance of medical devices

for regulatory purposes. The princi-

ples also apply to all other clinical

investigations and should be fol-

lowed as far as possible, depending

on the nature of the clinical investi-

gation and the requirements of na-

tional regulations.

This standard also specified general

requirements intended to protect the

rights, safety and well-being of hu-

man subjects; ensure the scientific

conduct of the clinical investigation

and the credibility of the results;

define the responsibilities of the

sponsor and principal investigator;

and assist sponsors, investigators,

ethics committees, regulatory au-

thorities and other bodies involved in

the conformity assessment of medi-

cal devices.

WSMI Chairmanship

handover

Celebrating 50 years

of success

50th AESGP Annual Meeting | 18th WSMI General Assembly

London | 3-5 June 2014

See pages 3-12 for the conference report

Hubertus Cranz, Tony Jamison, Johannes Burges, Jack Markley,

Hans van Zoonen, Akira Uehara, Gerhard Stummerer, Zhenyu

Guo, Hans Regenauer, Albert Esteve

Sheila Kelly honoured for 25 years of service to the self-care

sector

A change in leadership for WSMI took place at the

meeting with Zhenyu Guo handing over the association’s

Chairmanship to Erica Mann, Head of Consumer Care

Division, Bayer Healthcare. Mann thanked Guo for the

service to the self-care sector over the past years and

declared industry’s commitment for further support to the

development of self-care.

The closing event of the meeting at the Tower of London

provided the occasion to reflect on the developments in

the sector over the past years and to acknowledge the

significant contribution of key figures in the sector (see

picture above).