better medicines for children. from concept to reality

8102019 Better Medicines for children From Concept to Reality

httpslidepdfcomreaderfullbetter-medicines-for-children-from-concept-to-reality 136

Better

Medicinesfor Children

FromConcept to

RealityPROGRESS REPORTON THE PAEDIATRICREGULATION 983080EC983081Ndeg19012006

COM 9830802013983081 443FINAL

Health and

Consumers





REPORTFROM THECOMMISSIONTO THE

EUROPEANPARLIAMENTAND THECOUNCIL

Better Medicinesfor ChildrenFrom Concept to Reality

General Report on

experience acquired as a

result of the application

of Regulation (EC)ndeg 19012006 on

medicinal products for

paediatric use

(text with EEA relevance)





5

1IntroductionlsquoBetter Medicines or Childrenrsquo was the

ambitious title o a consultation papero February 2002 in which the European

Commission presented its vision or regu-

latory actions on paediatric medicinal

products1 At that time many o the prod-

ucts used in children were not specifically

studied or authorised in children Instead

doctors ofen used products authorised

or adults sometimes in different dosag-

es with the associated risks o inefficacy

andor adverse reactions

The consultation paper built on a 5-year

discussion process that started in 1997

with a round table meeting at the prem-

ises o the European Medicines Agency

(EMA) and was the blueprint or the sub-

sequent legislative act It outlined many

o the measures that are to be ound in

the Paediatric Regulation (Regulation (EC)

No 19012006 o the European Parlia-

ment and o the Council on medicinal

products or paediatric use2

hereinaferlsquothe Regulationrsquo)

The Regulation was adopted some five

years afer the consultation paper on 12

December 2006 It entered into orce on

26 January 2007 and its main provisions

were applicable rom 26 July 2008 (Ar-

ticle 7) and 26 January 2009 (Article 8)

respectively

Five years on it is time to take stock o

developments and report to the EuropeanParliament and the Council on the experi-

ence acquired as a result o the Regula-

tion in accordance with its Article 50(2)

Are we already seeing the emergence o

lsquobetter medicines or childrenrsquo

This report does not yet provide compre-

hensive answer as it is subject to certain

limitations it should thereore be regard-

ed as an interim report that presents a

first impression o the experience gainedIn view o the development cycles o me-

dicinal products it will take at least 10

years to gain a ull understanding o the

impact o the legislation This actor has

already been accounted or in the legis-

lation which requires the Commission to

provide a second more comprehensive

report in 2017 which in accordance with

Article 50(3) o the Regulation must in-

clude an analysis o the economic impact

o the rewards and incentives together

with an analysis o the Regulationrsquos im-

plications or public health with a view to

proposing any necessary amendments

However at this stage some analyses and

interim conclusions can be made

This document has been prepared in con-

sultation with Member States the EMA

and interested parties The Commission

particularly values the lsquo5-year Report to

the European Commissionrsquo presenting the

views o the EMA and its Paediatric Com-

mittee3 and the responses to the public

consultation the Commission undertook

at the end o 20124

1 httpeceuropaeuhealthfilespharmacosdocs

doc2002ebcd_pediat-rics_enpd

2 OJ L 378 27122006p 1 amended by Regulation

(EC) No 19022006 o theEuropean Parliament and othe Council o 20 December

2006 OJ L 378 27122006p 20

3 5-year report to theEuropean Commission mdashGeneral report on experience

acquired as a result o theapplication o the Paedi-

atric Regulation preparedby the European MedicinesAgency with its Paediatric

Committee httpeceuropa

euhealthfilespaediat-rics2012-09_pediatric_re-

port-annex1-2_enpd

4 httpeceuropaeuhealth

human-usepaediatric-med-icinesdevelopments2013_

paediatric_pc_enhtm



6

2The Paediatric

RegulationIn 2010 around 21 o Europeans were

children representing more than 100 mil-

lion people Children represent a vulnera-

ble population group with developmental

physiological and psychological differenc-

es rom adults They are not merely lsquosmall

adultsrsquo Age- and development-related

research and the availability o suitable

medicinal products is consequently par-

ticularly important

Studies carried out beore the Regulation

was adopted showed that over 50 o the

medicines used or children had not been

tested or use in this specific age group

What is more only a limited number o

medicinal products had been developed

specifically with children in mind Com-

panies had already developed a range o

products against a number o diseases

prior to the Paediatric Regulation particu-

larly in sectors such as childhood immuni-sation by means o vaccines However the

availability o child-appropriate medicines

was generally unsatisactory Accordingly

the Regulation was seen as a response to

the absence o sufficient numbers o suit-

able authorised medicinal products with

appropriate dosages and pharmaceutical

orms to treat conditions in children in the

European Union (EU)

There are several reasons or the lacko paediatric medicines It would how-

ever be too simplistic to pin the blame

on pharmaceutical companies or not car-

rying out enough research and develop-

ment (RampD) to adapt medicinal products

to the needs o the paediatric popula-

tion This reluctance has long mirrored a

general social and ethical paradigm that

children should be protected rom clinical

research Only in the last two decades has

there been a shif to the current consen-sus o better protecting children through

clinical research

Economic actors certainly rendered pae-

diatric RampD less attractive in terms o

achieving an adequate return on invest-

ment Children are not a homogenous

sub-group mdash subpopulations range rom

neonates to teenagers with different bio-

logical and pharmacological characteris-

tics Age-appropriate research makes the

process more expensive and complex or

organisations that are active in this sec-

tor

However the absence o specifically

tested products ofen lef healthcare

proessionals with no alternative but to

use products lsquooff-labelrsquo with the associ-

ated non-negligible risks o inefficacy or

adverse reactions Such a situation was

contrary to the general goal to providehigh-quality medicinal products to the en-

tire EU population

To address this problem the Regula-

tion establishes a system o obligations

rewards and incentives together with

horizontal measures to ensure that medi-

cines are regularly researched developed

and authorised to meet the therapeutic

needs o children Other than the Orphan

Regulation5

which is limited to providingvarious incentives the Paediatric Regula-

tion has a direct impact on companiesrsquo

RampD expenditure While not questioning

that medicinal development is company

driven it compels companies to consider

the potential paediatric use o medicinal

products they develop

5 Regulation (EC)Ndeg 1412000 o the Euro-

pean Parliament and theCouncil o 16 December

1999 on orphan medicinalproducts OJ L 18 2212000p 1



7

The key objectives of theRegulation are

bull to ensure high-quality research into

the development o medicines or

children

bull to ensure over time that the major-ity o medicines used by children are

specifically authorised or such use

with appropriate orms and ormula-

tions

bull to ensure the availability of high-

quality inormation about medicines

used by children

The key measures included inthe Regulation are

bull setting up an expert committee with-

in the EMA the Paediatric Commit-

tee

bull requiring companies to submit dataon the use o a medicine in children

in accordance with an agreed paedi-

atric investigation plan when apply-

ing or marketing authorisation or

medicines and line-extensions or

existing patent-protected medicines

bull a system of waivers from the re-

quirement or medicines unlikely to

benefit children and a system o de-

errals in relation to the timing o the

requirement to ensure that medi-

cines are tested in children only whenit is sae to do so and to prevent the

requirements delaying the authorisa-

tion o medicines or adults

bull a reward for complying with the re-

quirement in the orm o a six-month

extension to the Supplementary Pro-

tection Certificate

bull a reward in respect of orphan medi-

cines or compliance in the orm o

an extra two years o market exclu-

sivity added to the existing ten yearsawarded under the EUrsquos Orphan Reg-

ulation

bull a new type of marketing authorisa-

tion the Paediatric Use Marketing

Authorisation (PUMA) to attract newpaediatric indications or off-patent

products

bull measures to maximise the impact of

existing studies on medicines or chil-

dren

bull an EU inventory of the therapeuticneeds o children to ocus the re-

search development and authorisa-

tion o medicines

bull an EU network of investigators and

trial centres to carry out the required

RampD

bull a system of free scientic advice for

the industry provided by the EMA

bull a public database of paediatric stud-

ies

bull a provision on EU funding for re-search to stimulate the development

and authorisation o off-patent med-

icines or children



8

The Regulation gives the EMA and its

Paediatric Committee primary responsi-

bility or handling paediatric investigation

plans deerrals and waivers This provides

the Agency with concrete decision-mak-

ing powers

The operational costs o the PaediatricRegulation are partly covered by a contri-

bution rom the EU budget (see Table 8)

as its main activities do not attract any

ees For the period 2007-12 the EU

budget contribution amounted to more

than EUR 39 million In addition Member

Statesrsquo national competent authorities

contribute resources in kind especially

staff time or the assessment o paediat-

ric investigation plans (see Table 12)







11

cantly (see Table 5) despite the act that

issues o pharmaceutical non-clinical and

clinical development are also part o the

discussions o a paediatric investigation

plan To acilitate collaboration with the

Paediatric Committee joint procedures

have been created within the EMA

413 Clinical trials with children

Medicines or use in children need to be

tested with appropriate ormulations in

the paediatric population to ensure their

sae and effective use Hence it is gener-

ally accepted that the Paediatric Regula-

tion will lead to more clinical trials in chil-

dren The figures in the EudraCT database

have not yet shown an increase in paedi-

atric trials The number remained stablebetween 2006 and 2012 averaging 350

trials per year with some fluctuations (see

Table 6) It should be pointed out how-

ever that while the number o paediat-

ric trials remained stable the number o

clinical trials in all populations decreased

between 2007 and 2011

Moreover until recently EudraCT was lim-

ited to paediatric trials commencing in the

EU Data on paediatric trials that are parto a paediatric investigation plan and con-

ducted outside the EU have only become

publicly available since spring 2011

It should also be noted that the initiation

o a considerable percentage o clinical

trials included in a paediatric investiga-

tion plan has been deerred in order to

avoid delays in the authorisation o the

corresponding product or adults Hence

the impact o the Paediatric Regulation on

paediatric trials will become more appar-

ent in EudraCT in the years to come There

has however been an evident increase in

the number o paediatric study partici-

pants in particular or the age group rom

0 to 23 months who were normally not

included in trials prior to 2008 (see Ta-

ble 7) Allowing neonates and inants to

benefit rom research is a positive sign

as these have been the most neglected

groups so ar



12

414 Optimised framework and

coordination

The Paediatric Regulation osters a com-

prehensive network o expertise in paedi-

atric matters within the EU In this context

the role o the Paediatric Committee ispivotal as it brings together a high level

o expertise and competence

The Committee has contributed to the

scientific guidelines published by the EMA

and has so ar convened 22 expert work-

shops on the development o medicines

or children

In addition the European Network or

Paediatric Research at the EMA (Enpr-

EMA) was established in 2009 While aclosely-knit network o experts existed

prior to the introduction o the Regula-

tion in disease areas such as paediatric

oncology Enpr-EMA provides the added

value o a holistic approach by bringing

together national and European networks

investigators and centres with specific ex-

pertise in designing and conducting high-

quality studies in children

However question still remain as towhether this expertise translates into su-

ficient capacity within the EU to conduct

trials in specialised investigation settings

Well-developed research networks capa-

ble o acilitating the necessary research

to ulfil the commitments included in

paediatric investigation plans do exist in

some but not all Member States

415 International cooperation

On an international level the EMA has de-veloped international links with medicines

agencies in the United States Canada

and Japan O particular interest is the

cooperation with the US Food and Drug

Administration given that already in the

late 1990s the United States introduced

legislation that stimulated the develop-

ment o medicinal products or paediatric

use by means o a combination o incen-

tives and obligations This cooperation is

also o great interest to stakeholders as

it may give companies the possibility o

satisying the legislation in both regions

with the same studies

In addition the EMA participates actively

in the Paediatric medicines regulatory

network16 which was created in 2010 as

part o the WHOrsquos Better Medicines or

Children initiative

42 More medicines available

for children

Over 12 years (rom 1995 to 2006) 108

o all 317 indications o 262 centrally au-

thorised medicines included the paediat-

ric population Since the Paediatric Regu-

lation entered into orce 31 out o 152

new medicines have been authorised or

paediatric use 10 o which met the con-

ditions o Article 7 This is not more than

a lsquosnapshotrsquo o the effects o the Regula-

tion as this figure is likely to increase inthe uture as a considerable number o

the new already authorised medicines

are subject to an investigation plan where

completion was deerred to avoid delays

in the authorisation o the adult product

It ollows that in the years to come many

more o those 152 new medicines are ex-

pected to be authorised or paediatric use

Annual reports on deerred paediatric

studies o authorised medicines indicate

that the majority o paediatric investiga-tion plans are running to schedule Pae-

diatric research is on-going at the same

rate across therapeutic areas such as on-

cology vaccines and immunology-rheu-

matology-transplantation

Furthermore by the end o 2011 72 new

paediatric indications had been approved

or medicines already authorised includ-

ing 30 indications (18 centralised) arising

rom the obligation in Article 8 Moreover26 new pharmaceutical orms were au-

thorised or paediatric use including 18

adapted orms or centrally authorised

medicines

As ar as Paediatric Use Marketing Au-

thorisation is concerned to date only one

authorisation has been granted This alls

short o initial expectations

16 httpwwwwhointchild-medicinespaediatric_regula-

torsen



13

A detailed inventory o centrally autho-

rised products is provided in Annex II

Rewards and incentives

Companies that have complied with the

obligations o the Regulation may benefit

rom a reward once the product concerned

is authorised or the product inormation isamended The reward takes the orm o a

6-month extension o the supplementary

protection certificate (SPC) provided or

by Regulation (EC) No 469200917 or in

the case o an orphan medicinal product

by an extension o the ten-year period o

orphan market exclusivity to twelve years

No orphan rewards have been awarded

yet In this regard it is observed that some

companies withdrew the orphan designa-tion o a product in order to qualiy or

the SPC reward rather than the orphan

reward which seems to be more attrac-

tive rom an economic perspective As ar

as SPC extensions are concerned national

patent offices in 16 Member States had

by the end o 2011 granted 6-month ex-

tensions to 11 medicinal products which

resulted in a total o more than 100 na-

tional SPCs

It should be pointed out that a ruling othe European Court o Justice urther

increased the value o the paediatric

reward as it made clear that the initial

certificate could have a negative or zero

duration which could then become posi-

tive once the paediatric extension was

granted18

43 Increased information on

medicines used in childrenTo provide better inormation on the use

o medicinal products in children Article

45 o the Paediatric Regulation requires

companies holding data on the saety

or efficacy o authorised products in the

paediatric population to submit these

studies to the competent authorities In

this way the data can be assessed and

where appropriate the authorised prod-

uct inormation amended Article 46 o

the Regulation also requires companies tosubmit newly generated paediatric data

Since 2008 more than 18 000 study re-

ports on roughly 2 200 medicinal prod-

ucts have been submitted revealing the

large amount o existing paediatric inor-

mation available at company level

These study reports have been and

continue to be assessed by the compe-

tent authorities thanks to an impressive

work-sharing project (see Tables 10 and11) For nationally authorised products

this has led to the publication o assess-

ment reports covering more than 140

active substances and in a considerable

number o cases to recommendations

or changes to the summaries o product

characteristics o authorised products re-

sulting in 65 actual changes For centrally

authorised products by 2011 the Agency

had completed the assessment o all the

data submitted under Article 45 covering55 active substances in 61 centrally ap-

17 Regulation (EC) No4692009 o the Euro-

pean Parliament and othe Council o 6 May 2009

concerning the supplemen-tary protection certificateor medicinal products OJ

L 152 1662009 p 1 ThisRegulation is a codificationo Council Regulation (EEC)

No 176892

18 Case C-12510 Merck

Sharp amp Dohme v DeutschesPatent- und Markenamt notyet published in the ECR

paragraph 37 lsquoi the SPCapplication had to be reused

because the calculationprovided or in Article 13(1)o Regulation No 176892

results in a negative or zero

duration the holder o thebasic patent could not obtain

an extension o protectionconerred by such a patenteven i it conducted all the

studies according to the ap-proved paediatric investiga-

tion plan under Article 36 oRegulation No 19012006Such a reusal would be

liable to adversely impacton the useul effect oRegulation No 19012006

and might jeopardise the

objectives o that regulationnamely the compensation

o effort made to evaluatethe paediatric effects o themedicinal product at issuersquo



14

proved medicinal products The summa-

ries o product characteristics o 12 me-

dicinal products were changed ollowing

the assessment

5Lessonslearnt51 Better access to

treatment

One o the explicit goals o the Paediatric

Regulation is to increase the number oproducts that are researched developed

and authorised or use in children and

to reduce the off-label use o medicinal

products in the paediatric population

The main tool to achieve this result is to

oblige companies to establish a paediat-

ric investigation plan or each newly de-

veloped product or or the line extension

o an already authorised product that is

still under patent protection The plan ismeant to ensure mdash under the supervi-

sion o the Paediatric Committee mdash that

the necessary data are generated so as

to determine the conditions under which

a medicinal product may be authorised

to treat children Since 2008 more than

600 paediatric investigation plans have

been approved However only a minor-

ity o them has been completed to date

the vast majority are still on-going This

is due to the long development cycles omedicinal products ofen lasting more

than a decade and the near-systematic

deerral o paediatric studies The high

number o deerrals may not have been

initially expected but are currently a real-

ity as or most o the medicinal products

that have been authorised so ar the RampD

programme started beore the entering

into orce o the Regulation Consequent-

ly the paediatric requirements could not

be taken into account rom the beginningo the product development

While the Paediatric Regulation has led

to some new authorisations that include

paediatric indications the regulatory in-

strument is recent and it will probably

take at least a decade beore it can be

judged in terms o its output In terms o

pharmaceutical orms there is however

already a visible positive impact

In this context criticism has been voiced

that the Regulation will ail to ensure abreakthrough in areas o particular pae-

diatric need such as paediatric oncology

This argument is related to the act that

the starting point or the majority o pae-

diatric investigation plans is an ongoing

RampD programme or a medicinal product

or adults An intrinsic consequence o this

approach is that these products primarily

target adult conditions They are devel-

oped in areas where there is a need (or a

market) in the adult population This needin the older population does not neces-

sarily correspond to the paediatric popu-

lationrsquos need

Moreover the Regulation grants waivers

rom its obligations where the disease or

condition or which the specific medicinal

product is intended occurs only in adult

populations This legislative approach cre-

ates riction in the case o diseases that

are specific and exclusive to children Italso limits the powers and possibilities o

the Paediatric Committee when reviewing

and agreeing to a paediatric investigation

plan as regards the scope o studies that

the Committee may request rom appli-

cants ollowing the objective and scien-

tific-based assessment o the compound

concerned19

These constraints and boundaries have to

be taken into account when judging the

impact the Regulation is likely to make In

addition the effect o instruments such as

the Orphan Regulation have to be consid-

ered given that or example all paediatric

cancers are rare diseases and all under

the EU policy ramework on rare diseases

All in all the achievements highlighted in

chapter 4 o this report and the number

o products with new paediatric indica-

tions show that there are some encourag-

ing signs afer this first five-year period it

is however too early or comprehensive

answers

19 Case T-5209 Nycomed vEMA not yet published

See the results o the publicconsultation conducted by

the Commission in prepara-tion o this Report



15

52 The PUMA concept a

disappointment

The Paediatric Regulation introduced a

new type o marketing authorisation mdash

the Paediatric Use Marketing Authorisa-

tion (PUMA) As an incentive to carry out

research into the potential paediatric use

o off-patent medicinal products that have

been authorised or adults this marketing

authorisation offers 8 years o data and

10 years o market exclusivity to any new

off-patent product developed exclusively

or use in the paediatric population Thus

the main goal o the PUMA concept is to

stimulate research in existing products

This scheme has been supported by EU

unding through the EU Framework Pro-

grammes or Research and Technological

Development

However to date only one PUMA has been

granted with a ew more projects cur-

rently in the pipeline

Neither industry nor academic networks

have embraced this opportunity as ully

as the Regulation intended It would seem

that the incentive o data and market ex-

clusivity does not work or these productsor at least that the market opportunities

in this sector are currently considered in-

sufficient to outweigh the inherent eco-

nomic risks o pharmaceutical develop-

ment Researchers are not engaging in

trials with medicines that have been on

the market or years Companies seem to

ear that market exclusivity will not pre-

vent physicians rom continuing to use

competitor products with the same active

ingredient off-label at lower costs or thatsubstitution or cheaper adult orms takes

place at the level o pharmacies Moreo-

ver national pricing and reimbursement

rules in Member States ofen do not al-

low or the additional research needed to

obtain the PUMA to be rewarded in price

negotiations20

Against this background the PUMA con-

cept has ailed so ar to ulfil the initial

expectationsThe EMA will in uture accept paediatric

investigation plans or a PUMA that cover

only certain age groups and not the en-

tire paediatric population This may offset

some o the reservations that currently

hamper better endorsement o the PUMA

concept

53 No impact on adultdevelopment

Studies prior to the adoption o the Regu-

lation have suggested a theoretical risk

that the requirements or research in chil-

dren could lengthen the overall drug de-

velopment process21 The Regulation has

met this risk head-on In order to avoid

any delays in authorising medicines or

other populations it allows or the grant-

ing o deerrals relating to the initiation orcompletion o some or all o the meas-

ures contained in a paediatric investiga-

tion plan

Experience shows that the deerral is a

widely used instrument which suggests

that the risk o delays in the processing o

adult applications is minimal There have

been some transitional problems in cases

where the adult programme was already

established when the Regulation enteredinto orce but these issues seem to have

been resolved

A concern that was raised initially was

that some companies would become

reluctant to develop new indications

pharmaceutical orms and new routes o

administration in small markets and or

products with low sales to avoid being

bound by the paediatric obligation under

Article 8 o the Regulation However thereis no evidence o such effect Moreover

it may also be argued that the incentive

o a potential six-month extension o the

SPC served to counterbalance such an

effect as it may have led companies to

examine more thoroughly the benefits o

a line extension taking into account the

economic value o the paediatric reward

Still industry stakeholders claim that

in rare cases the development or new

medicinal products has been delayedor abandoned in the expectation or as a

consequence o additional costs and re-

quirements associated with paediatric de-

20 See the results o thepublic consultation con-

ducted by the Commission inpreparation o this Report

21 C Commission StaffWorking Document Proposal

or a Regulation o the Euro-pean Parliament and o theCouncil on medicinal prod-

ucts or paediatric use andamending Council Regulation(EEC) No 17692 Directive

200183EC and Regula-tion (EC) No 7262004Extended impact assessment

(COM2004599F)



16

keting authorisation holders are obliged

to ensure that the product inormation

is kept up to date with the current scien-

tific knowledge While preerence should

be given to cooperative approaches the

enorcement tools may need to be used

i companies do not overcome their res-

ervations

On the whole the requirements o Articles

45 and 46 have provided an efficient and

appropriate instrument or collecting and

evaluating existing paediatric studies

55 Clinical trials with

children

It is generally accepted that the Paediatric

Regulation will lead to more clinical trialswith children but that its aims should be

achieved without subjecting children to

unnecessary clinical trials

The youngest paediatric-age subsets

including neonates are particularly sen-

sitive It will be a constant challenge to

balance the therapeutic needs o these

age groups with their specific vulnerability

when considering and deciding on the ap-

propriateness o specific clinical trials or

the specific settings o studies in this age

subset Efforts are thereore continuously

being made to explore alternative means

eg the use o extrapolation modelling

and simulation techniques to reduce the

number o study subjects as much as

possible The Paediatric Committee is ac-

tively contributing to acilitate the devel-

opment and use o such means including

non-conventional trial design

Another challenge is how to avoid dupli-cating trials or different paediatric inves-

tigation plans rom different applicants

Companies embarking on product devel-

opment in similar areas may be required

by the agreed paediatric investigation

plan to conduct studies within similar

settings While collaborative approaches

between companies would be highly de-

sirable and have occurred on rare occa-

sions they ofen conflict with companiesrsquo

understandable reluctance to share datawith competitors in the early stages o

product development and participate in

direct comparisons This situation could

velopment Overall there is however no

evidence that the Regulation has a con-

siderable negative impact on products or

other populations

Rather there are some concerns that the

requirements under the Regulation may

cause delays in the authorisation o prod-ucts with paediatric-only indications as

they bring added complexity to the RampD

and regulatory process or products that

already directly target children The added

value o the submission o a paediatric in-

vestigation plan in these cases will be as-

sessed urther in the 2017 report

54 Reaping the benefits of

existing information

There was widespread speculation prior to

the adoption o the Paediatric Regulation

as to how many studies would be submit-

ted by pharmaceutical companies in ac-

cordance with Articles 45 and 46 The act

that competent authorities received more

than 18 000 studies reveals the consid-

erable amount o paediatric inormation

that existed at company level

Certainly it is true that not all the inor-

mation submitted met modern require-

ments or scientific data and clinical re-

search and that the work-sharing process

o evaluating the inormation is rather

long and resource intensive

Nevertheless compared to the PUMA con-

cept this scheme proved more successul

in terms o output and in recommending

and implementing changes to the sum-

mary o product characteristics o author-

ised products In its public consultationthe Commission called Articles 45 and 46

the lsquohidden gemsrsquo o the Regulation

One drawback that remains however

is reluctance by marketing authorisa-

tion holders to update the summary o

product characteristics on a voluntary

basis This said the Regulation contains

mechanisms to overcome such reluctance

as it empowers competent authorities to

directly update the summary and varythe marketing authorisation accordingly

Moreover in accordance with Article 23

o Directive 200183EC22 and Article 16

o Regulation (EC) No 726200423 mar-

22 Directive 200183EC othe European Parliament and

o the Council o 6 November2001 on the Community

code relating to medicinalproducts or human use OJ L311 28112001 p 67

23 Regulation (EC) No7262004 o the European

Parliament and o the Coun-cil o 31 March 2004 layingdown Community procedures

or the authorisation andsupervision o medicinalproducts or human and

veterinary use and establish-ing a European Medicines

Agency OJ L 136 3042004p 1



17

lead to competition among companies to

find investigators and study participants

as well as the duplication o trials which

are unnecessary rom a scientific and

ethical point o view

The Paediatric Committee is able to waive

paediatric trial requirements where thespecific medicinal product does not rep-

resent a significant therapeutic benefit

over an existing treatment or paediatric

patients including once the product is au-

thorised (Article 11) However this option

does not provide a way out in the early

stages o product development where

the Committee has to ensure equal treat-

ment and non-discriminatory approaches

The key to avoiding such unnecessary tri-

als is transparency with regard to ongoingand completed trials The situation contin-

ues to be monitored

Finally it is in the interest o the EU that

paediatric trials stemming rom paedi-

atric investigation plans are conducted

within the EU This has less to do with

the standards under which a trial is con-

ducted given that clinical trials carried

out outside the EU have to meet the ethi-

cal and scientific requirements o the EUprovisions on clinical trials24 than with the

act that studies within the EU may pro-

vide patients there with early access to

innovative medicines To date there is in-

sufficient data on the ratio between pae-

diatric trials conducted within and outside

the EU However in view o the upgraded

unctionalities o the EudraCT database it

is expected that more data will be avail-

able in 2017 or the second report

56 Spreading the news mdash

getting new information

to patients and healthcare

professionals

I the Regulation is to be a success it is

not only necessary that data on the use

o a specific product in the paediatric

population are collected but that these

data are then also appropriately commu-

nicated to and used by paediatricians intheir day-to-day work or the benefit o

their patients

In this regard some studies published in

the medical literature suggest a ailure

on the part o practitioners to recognise

the actual amount o off-label prescrib-

ing to children Moreover it is claimed that

the prescribing habits o practitioners are

ofen strongly influenced by personal ex-

perience rather than by evidence-based

inormation or paediatric medicine25

These studies in making generalisations

may not have taken into account the het-

erogeneity o healthcare proessionals

whose receptiveness varies greatly ac-

cording to their work setting and specific

area o specialisation At the same time

such observations may point to a sub-

stantial hurdle in achieving the goal o the

Paediatric Regulation

National competent authorities as well as

organisations or healthcare proessionals

seem particularly qualified to consider ap-

propriate ways o ensuring an adequate

flow o inormation Some Member States

have already established a number o

tools to communicate effectively and e-

ficiently with healthcare proessionals

eg by means o regular meetings web-

based inormation distribution systems ornational ormularies

57 Is the burden greater

than rewards

There can be no doubt that the Paediat-

ric Regulation places a considerable ad-

ditional burden on pharmaceutical com-

panies with its obligations regarding

research on products or use in children

However this approach was adopted be-cause market orces alone proved insu-

ficient to stimulate adequate research

The Regulation requires companies to

submit paediatric investigation plans at

an early stage o product development

However research on some active sub-

stances may be discontinued at later

stages should urther studies ail to show

potential with respect to the saety and

efficacy o the product For every success-

ul authorised medicinal product there aremany that ail to make the finishing line

Hence not all approved paediatric investi-

gation plans will be completed as compa-

24 Directive 200120EC othe European Parliament

and o the Council on theapproximation o the laws

regulations and administra-tive provisions o the Mem-ber States relating to the

implementation o good clini-cal practice in the conducto clinical trials on medicinal

products or human use OJ L121 152001 p 34

25 5-year report to theEuropean Commission (seeootnote 3) page 41



18

nies may decide to stop the correspond-

ing adult development It is too early still

to obtain reliable statistics that show

the ratio between completed and non-

completed paediatric investigation plans

but in the current context not all approved

plans will eventually result in an approved

medicine with a paediatric indication

In terms o output this entails some un-

necessary effort in compiling and screen-

ing paediatric investigation plans To what

extent this is offset by the benefit o early

submission which ensures that the pae-

diatric development fits smoothly into the

overall product development need ur-

ther monitoring

A urther point o concern is the highnumber o modifications to paediat-

ric investigation plans Figures seem to

suggest that nearly all plans have to

be modified at least once Conceptually

though this does not come as a surprise

in view o the early submission o pae-

diatric investigation plans the length o

adult and paediatric developments and

the substantial deerrals granted An

RampD plan requently has to be adapted

or amended to take account o initial re-sults Recruitment problems or necessary

design changes in the trials may also lead

to modifications While it is acknowledged

that substantial amendments or modifi-

cations to the plan have to be subject to

discussions with the Paediatric Commit-

tee this is less obvious or minor changes

In this context the level o detail required

by the EMA has been repeatedly criticised

In the past five years the EMA and its

Paediatric Committee have made effortsto provide or some flexibility in the plan

so to allow a margin o manoeuvre that

takes account o uncertainties in relation

to certain parameters o a trial

In any case the Commission intends to

review its Communication on the ormat

and content o applications or agree-

ment or modification o a paediatric in-

vestigation plan to take into account the

experience gained including the consider-

able number o modification requests

On a positive note it can be noted that

companies are applying or the rewards

provided by the Regulation primarily the

6-month extension o the Supplementary

Protection Certificate which have been

introduced to offset the additional bur-

den The economic value o the reward

depends on the turnover o the product

concerned In the case o blockbuster

products the amount may be consider-

able while or niche products the effect

is small

An in-depth evaluation o the economic

impact will be included in the 2017 report

in order to draw conclusions on the bal-

ance between burden and rewards and

public health benefits



19

6Outlook mdash

A fairy-taleending aheadlsquoBetter Medicines or Children mdash From

Concept to Realityrsquo is the title o this re-

port Readers may suggest that based on

the evaluation reerred to above it would

be more appropriate to add a question

mark It is evident that it is too early still

to make a firm statement Despite more

than five years o experience the true im-pact o the Regulation on the health o

children will only become apparent over

time as experience is accumulated in the

longer term

There are encouraging signs though

Paediatric development has become a

more integral part o the overall develop-

ment o medicinal products in the EU A

number o new products with paediatric

indications and age-appropriate pharma-ceutical orms have been authorised and

made available to patients A high num-

ber o agreed paediatric investigation

plans indicates that urther products are

in the pipeline

However it needs to be pointed out that it

would be wrong to expect the Regulation

to be able to solve all problems Instead

it is a major catalyst to improve the situ-

ation o young patients

Finally some weaknesses and deficits

have also become apparent in the last

five years Their impact on the overall

perormance o the Regulation has to be

closely monitored On the basis o the ac-

tions outlined above the Commission in-

tends to fine-tune the current implemen-

tation together with the EMA

Even i better medicines or children are

not yet a reality it should be the ambitiono all stakeholders involved that this piece

o legislation will be or the greater good

o children so that in the 2017 report

the discussion will ocus not on whether a

question mark should be added to the ti-

tle o the report but on whether it should

be an exclamation mark instead





21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables

Table 1Agreed paediatric investigations plans (PIPs) 2007-2012

0

50

100

150

200

250

2007 2008 2009 2010 2011 2012

Agreed PIPs (total number)

Agreed PIPs submitted under Article 7 (without waivers)


Source EMA Paediatric database The numbers on agreed PIPs correspond to EMA decisions

Table 2Agreed paediatric investigations plans (PIPs) compared to ull waivers and modifications 2007-2012

0

50

100

150

200

250

2007 2008 2009 2010 2011 2012


Submitted modifications of an agreed PIP

Agreed Full waivers

Source EMA Paediatric database The numbers on agreed PIPs and waivers correspond to EMA decisions





25

Table 5Scientific advice and protocol assistance including ollow-ups (provided by the EMA Scientific Advice Working

Party and the Committee or Human Medicinal Products per year)

259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012

Total number of advice (Scientific Advice and Protocol Assistance)

Sum of paediatric-only and mixed (adult and paediatric development questions)

advice

Paediatric-only or mixed advice that involved a Paediatric Committee member(s) as

expert(s)

Source EMA databases Year o advice letter

Year o start o procedure

Table 6Paediatric clinical trials by year o authorisation

2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials

that are part of anagreed PIP 2 1 2 6 16 30 76 76

Proportion of

paediatric trials

that are part of an

agreed PIP among

paediatric trials 1 0 1 2 4 8 23 23

Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of

paediatric trials of

all trials 8 8 7 8 9 10 9 9

Source EudraCT Data Warehouse using a predefined query on 6 March 2013 and counting the first authorised trial only in the case o more thanone Member State This partial inormation requires sponsors to use a Clinical Trial Application orm that was only available rom November 2009 or use with version 8 o EudraCT

(available rom 2011)



26

Table 7Number o children to be enrolled in clinical trials

Number

of subjects 2006 2007 2008 2009 2010 2011 2012

Pretermnewborns 0 0 0 207 82 2 281 1 712

Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference

number of paediatric

trials 316 355 342 404 379 334 332

Source EudraCT Data Warehouse using a pre-defined query on 6 March 2013 modified by excluding studies or lsquoimmunological medicinal productsrsquo

Table 8EU budget contribution to the Paediatric Regulation and the EMA expenditure

0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012

EU budget contribution (in Million euro)

EMA expenditure for paediatri cs (in Mill ion euro)

EMA expenditure for paediatr ics including support (in Million euro)



27

Table 9Percentage o European Medicines Agencyrsquos human resources working in the paediatric area rom 2006 (inner

circle) to 2012 (outer circle)

733 (2012)

052 (2006)

Table 10Member States acting as rapporteurs or the assessment o studies submitted in accordance with Article 46

(paediatric work-sharing procedures)

0

10

20

30

40

50

60

UK DE SE NL FR DK IT BE PL ES NO SK FI IE RO AT HU EL CZ PT LV BG

Study included in worksharing Rapporteur appointed



28

Table 11Member States acting as rapporteur or the assessment o studies submitted in accordance with Article 45


0

10

20

30

40

50

60

UK DE NL DK AT FR PL SE ES IE CZ MT IT BE SI EE FI HU NO RO BG EL LV PT IS SK

Wave 1 Wave 2 Wave 3 Wave 4 Wave 5 Wave 6 Wave 7 Wave 8 Wave 9


Table 12Member States acting as rapporteurspeer reviewers in EMArsquos Paediatric Committee procedures (initial PIP

waiver or modification o an agreed PIP)

0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s

C z e c h R e p u b l i c

D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e

H e a l t h c a r e a n d

A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y

P a t i en t s Or g a ni s a t i on

P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en

T h eN e t h er l a n d

s

U ni t e d K i n g d om

Initial PIP applications PIP modifications



29

ANNEX II

Detailed inventory of centrally authorised medicinalproducts for paediatric use since the entry into force

of the Paediatric Regulation

Table 13Medicinal products authorised centrally since 2007 which include a paediatric indication

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only

or lsquomixedrsquo (adult

and paediatric)

Retapamulin Altargo 2007 No Mixed

Nelarabine Atriance 2007 No Mixed

Human papillomavirus vaccine[types 16 18] Cervarix 2007 No Mixed

Hydroxocobalamin Cyanokit 2007 No Mixed

Idursulase Elaprase 2007 No Mixed

Gadoversetamide Optimark 2007 No Mixed

Betaine anhydrous Cystadane 2007 No Mixed

Stiripentol Diacomit 2007 No Paediatric only

Mecasermin Increlex 2007 No Paediatric only

Rufinamide Inovelon 2007 No Mixed

Hydroxycarbamide Siklos 2007 No Mixed

Human normal

immunoglobulin (ivig) Flebogamma DIF 2007 No Mixed

Fluticasone uroate Avamys 2008 No Mixed

Human normal immunoglobulin Privigen 2008 No Mixed

Lacosamide Vimpat 2008 No Mixed

Micaungin Mycamine 2008 No Mixed

Sapropterin Kuvan 2008 No Mixed

Sugammadex Bridion 2008 No Mixed

Tocoersonal d-alpha

tocopheryl polyethylene glycol

succinate Vedrop 2009 No Paediatric only

Miamurtide Mepact 2009 No Mixed

Rilonacept Rilonacept Regeneron 2009 No Mixed

Tacrolimus Modigra 2009 No Mixed

Pneumoccocal polysaccharideconjugate vaccine (adsorbed) Synflorix 2009 No Paediatric only

Canakinumab

Ilaris (PIP not yet

completed) 2009 Yes Mixed



30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)

Pneumoccocal polysaccharide

conjugate vaccine (13-valentadsorbed)

Prevenar 13 (PIP not yetcompleted) 2009 Yes Paediatric only

Meningococcal group a c

w135 and y conjugate vaccine Menveo 2010 Yes Mixed

Velaglucerase ala

Vpriv (PIP not yet


Influenza vaccine (live

attenuated nasal) Fluenz (Waiver) 2011 Yes Paediatric only

C1 inhibitor human

Cinryze (PIP not yet


Dihydroartemisinin

piperaquine phosphate

Eurartesim (PIP not yet


Midazolam Buccolam 2011 Yes (PUMA) Paediatric only

EverolimusVotubia(PIP not yet completed) 2011 Yes Mixed

Tobramycin

Tobi Podhaler (PIP not

yet completed) 2011 Yes Mixed

Nomegestrol estradiol Ioa Zoely 2011 Yes Mixed

Colistimethate sodium Colobreathe 2012 Yes Mixed

Mercaptopurine Xaluprine 2012 No Mixed

Catridecacog NovoThirteen 2012 Yes MixedEavirenz Eavirenz Teva 2012 No Mixed

Ivacafor Kalydeco 2012 Yes Mixed

Desloratadine Desloratadine ratiopharm 2012 No Mixed

Desloratadine Desloratadine Actavis 2012 No Mixed

Perampanel Fycompa 2012 Yes Mixed



31

Table 14List o centrally authorised medicinal products or which the therapeutic indication was extended to or amend-

ed or the paediatric population

Active substance(s)

Trade

name Date Subject of the extension

Levetiracetam Keppra

2007

2009

Extension o the indication to include adjunctive ther-

apy in the treatment o primary generalised tonic-

clonic (PGTC) seizures in adults and adolescents rom

12 years o age with idiopathic generalised epilepsyExtension o indication to include the adjunctive

treatment o partial seizures with or without second-

ary generalisation in children rom 1 month to lt4

years old

Pneumococcal sac-

charide conjugated

vaccine adsorbed Prevenar 2007

Extension o the indication to include new inorma-

tion on efficacy against disease caused by Strepto-

coccus pneumoniae serotypes 4 6B 9V 14 18C 19F

and 23F in otitis mediaExtension o indication rom active immunisation

against bacteraemic pneumonia to active immunisa-

tion against pneumonia

Infliximab

Remi-

cade 2007

Extension o indication to include treatment o

severe active Crohnrsquos disease in children aged 6 to

17 years

Darbepoetin ala Aranesp 2007

Extension o indication or CRF patients whichrestricted the use o Nespo to paediatric subjects ge

11 years o age

Fosamprenavir Telzir 2007

Extension o indication o Telzir in combination withritonavir or the treatment o Human Immunodefi-

ciency Virus Type 1 (HIV-1) inected adults in combi-nation with other antiretroviral medicinal products to

include paediatric populations

Lamivudine zidovu-

dine Combivir 2007

Extension o indication to include paediatric patients

and replacement o film-coated tablets by scored

film-coated tablets

Desloratadine Aerius 2007Extension o indication rom lsquochronic idiopathic urti-cariarsquo to lsquourticariarsquo

Insulin glulisine Apidra 2007

Extension o indication to include 6 year olds and

older children based on the results o 2 paediatricstudies

Human papilloma virusvaccine [types 6 11

16 18] (recombinantadsorbed) Gardasil 2008

Extension o indication to include the prevention ohigh-grade vaginal dysplastic lesions (VaIN 23)

Adalimumab Humira 20082011

Extension o indication to include treatment o active

polyarticular juvenile idiopathic arthritis in adoles-cents rom 13 to 17 years o age


polyarticular juvenile idiopathic arthritis in the paedi-

atric population aged rom 4 to 12 years

Caspoungin Cancidas 2008

Extension o the indication to include the paediatric

population



32

Active substance(s)

Trade


Etanercept Enbrel 20082011

Extension o indication to include the treatment

o chronic severe plaque psoriasis in children and

adolescents rom the age o 6 years who areinadequately controlled by or are intolerant to other

systemic therapies or phototherapies

Extension o indication to include lower age range

or polyarticular juvenile idiopathic arthritis lsquorom the

age o 4 yearsrsquo to lsquorom the age o 2 yearsrsquo

Miglustat Zavesca 2009

Extension o indication to include the treatment o

progressive neurological maniestations in adult

patients and paediatric patients with Niemann-Pick

type-C disease

Tacrolimus Protopic 2009

Extension o indication to lsquomaintenance treatmentrsquo

urther to completion o one study in adult patients

and one in paediatric patients

Tipranavir Aptivus 2009


HIV-1 inection in highly pre-treated adolescents 12years o age or older with virus resistant to multiple

protease inhibitors

Omalizumab Xolair 2009

Extension o indication to children rom 6 to lt12

years o age as add-on therapy to improve allergic

asthma control

Aripiprazole Abiliy 2009


schizophrenia in adolescents 15 years and older

Pegintereron ala-2b

PegIn-

tron 2009

Extension o indication o the combination therapypegintereron ala-2b and ribavirin to include treat-

ment o the paediatric population

Ribavirin Rebetol 2009



Abatacept Orencia 2010


moderate to severe active polyarticular juvenile idio-pathic arthritis in paediatric patients 6 years o age

and older who have had an insufficient response to

other DMARDs including at least one TNF inhibitor

Atazanavir sulphate Reyataz 2010

Extension o indication or Reyataz capsules toinclude the treatment o HIV-inected children and

adolescents above the age o 6 in combination with

other antiretroviral medicinal products

Measles mumps andrubella vaccine (live)

M-M-RVAXPRO 2010

Extension o indication to include administration tohealthy children rom 9 months o age

Nitric oxide Inomax 2011


pulmonary hypertension peri- and post heart surgeryin children

Tenoovir disoproxilumarate Viread 2011

Amendment o indication based on the results o a

saety and efficacy study in treatment-experiencedadolescents aged 12 to 18 years old

Paliperidone Invega 2011

Extension o indication to include treatment o psy-

chotic or manic symptoms o schizoaffective disorder

Sildenafil Revatio 2011

Extension o indication in paediatric patients aged

1 year to 17 years old with pulmonary arterial hyper-tension

Human normal immu-

noglobulin (ivig) Kiovig 2011

Extension o indication to include treatment o multi-

ocal motor neuropathy and hypogammaglobulinae-

mia in patients afer allogeneic haematopoietic stem

cell transplantation in adults and children



33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011

Extension o indication to include treatment o ac-

tive systemic juvenile idiopathic arthritis in patients

2 years o age and older who have respondedinadequately to previous therapy with NSAIDs and

systemic corticosteroids

Pneumococcal polysac-

charide conjugatevaccine (adsorbed) Synflorix 2011

Extension o indication to increase the upper agelimit o inants and children rom 2 years to 5 years

Insulin detemir Levemir 2011

Extension o indication as add-on therapy to liraglu-

tide treatment

Extension o indication to children aged 2-5 years

Eculizumab Soliris 2011

Extension o indication to include atypical haemolytic

uremic syndrome (aHUS) Additional vaccination and

antibiotic prophylaxis recommendation have alsobeen added in section 42 or treatment o aHUS in

adults and children

Human papillomavirus

vaccine [types 16 18](recombinant adju-

vanted adsorbed) Cervarix 2011 Extension o indication to children rom 9 years


Extension o the Juvenile idiopathic arthritis (JIA)indication to include children and adolescents with

extended oligoarticular JIA rom the age o 2 years

children and adolescents with enthesitis-related

arthritis rom the age o 12 years and children and

adolescents with psoriatic arthritis rom the age o12 years

Measles mumps

rubella and varicellavaccine (live) Proquad 2012

Extension o the age range in the indication to chil-

dren rom 9 months o age onwards under specialcircumstances ie outbreak control

For a more detailed inventory including inormation on nationally authorised products and new routes o

administration or new pharmaceutical orms please reer to Annex II o the lsquo5-year Report to the European

Commissionrsquo o the EMA














General Report on





paediatric use






5






























respectively



































at the end o 20124





2006 OJ L 378 27122006p 20






port-annex1-2_enpd



paediatric_pc_enhtm



6

2The Paediatric










ticularly important



















European Union (EU)












clinical research











tor








tire EU population








Regulation5













7




children




tions



used by children




tee


















tection Certificate





ulation




products



dren



tion o medicines



RampD




ies



icines or children



8






ing powers

















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps

















5






























respectively



































at the end o 20124





2006 OJ L 378 27122006p 20






port-annex1-2_enpd



paediatric_pc_enhtm



6

2The Paediatric










ticularly important



















European Union (EU)












clinical research











tor








tire EU population








Regulation5













7




children




tions



used by children




tee


















tection Certificate





ulation




products



dren



tion o medicines



RampD




ies



icines or children



8






ing powers

















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















6

2The Paediatric










ticularly important



















European Union (EU)












clinical research











tor








tire EU population








Regulation5













7




children




tions



used by children




tee


















tection Certificate





ulation




products



dren



tion o medicines



RampD




ies



icines or children



8






ing powers

















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















7




children




tions



used by children




tee


















tection Certificate





ulation




products



dren



tion o medicines



RampD




ies



icines or children



8






ing powers

















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















8






ing powers

















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps



















11














































groups so ar



12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















12


coordination










or children







































Children initiative


for children

Over 12 years (rom 1995 to 2006) 108































medicines






torsen



13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















13

























tional SPCs







granted18




































No 176892
















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















14




the assessment


treatment





















































lationrsquos need














concerned19















answers






15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















15


disappointment

















Development
























negotiations20









concept












tion plan








been resolved



























(COM2004599F)



16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















16








ervations






children






































other populations




















































Agency OJ L 136 3042004p 1



17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















17


















ues to be monitored





















professionals







their patients






























than rewards



























18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















18
















ther monitoring











































is small








19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















19

6Outlook mdash











longer term










in the pipeline


























21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps

















21

ANNEXES

Figures and Tables



22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















22



23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















23

ANNEX I

Figures and Tables


0

50

100

150

200

250

2007 2008 2009 2010 2011 2012






0

50

100

150

200

250

2007 2008 2009 2010 2011 2012



Agreed Full waivers






25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps

















25



259

277321

388 400 433 420

021 32

74 8057

91

0 0 0

68 8067

94

0

100

200

300

400

500

2006 2007 2008 2009 2010 2011 2012



advice


expert(s)




2005 2006 2007 2008 2009 2010 2011 2012

Paediatric trials

(number) 254 316 355 342 404 379 334 332

Paediatric trials


Proportion of

paediatric trials

that are part of an

agreed PIP among


Total number

of trials (adults

and or children) 3 350 3 979 4 749 4 512 4 445 4 026 3 809 3 698

Proportion of


all trials 8 8 7 8 9 10 9 9





26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















26


Number

of subjects 2006 2007 2008 2009 2010 2011 2012


Newborns 0 0 5 64 169 1 105 1 172

Infants and

toddlers 330 21 20 59 351 2 788 3 141

Children 2 142 181 200 2 230 2 055 10 325 20 677

Adolescents 368 111 205 1 577 2 861 9 054 13 193

Sum of

above 2 840 313 430 4 137 5 517 25 553 39 895

Reference


trials 316 355 342 404 379 334 332



0

1

2

3

4

5

6

7

8

9

10

2006 2007 2008 2009 2010 2011 2012






27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















27



733 (2012)

052 (2006)



0

10

20

30

40

50

60





28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















28



0

10

20

30

40

50

60






0

50

100

150

200

250

300

350

400

450

500

A u s t r i a

B el gi um

B ul g a r i a

C y pr u s


D enm a r k

E s t oni a

F i nl a n d

F r a n c e

G er m a n y

G r e e c e


A c a d emi a

H un g a r y

I c el a n d

I r el a n d

I t a l y

L a t vi a

L i t h u a ni a

L ux em b o ur g

M a l t a

N or w a y


P ol a n d

P or t u g a l

R om a ni a

S l ov a k i a

S l ov eni a

S p a i n

S w e d en


s





29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















29

ANNEX II




Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)












Human normal








Tocoersonal d-alpha







Canakinumab

Ilaris (PIP not yet




30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















30

Active

substance(s)

Trade

name

Year

of

authorisation

Requirement

to fulfil

Paediatric

Regulation

at first

authorisation

Indication is

paediatric-only


and paediatric)






Velaglucerase ala

Vpriv (PIP not yet




C1 inhibitor human



Dihydroartemisinin






Tobramycin













31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















31



Active substance(s)

Trade



2007

2009







years old

Pneumococcal sac-

charide conjugated








Infliximab

Remi-

cade 2007



17 years



11 years o age





Lamivudine zidovu-

dine Combivir 2007



film-coated tablets
















population



32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















32

Active substance(s)

Trade














type-C disease








protease inhibitors




asthma control




Pegintereron ala-2b

PegIn-

tron 2009
















M-M-RVAXPRO 2010














Human normal immu-








33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps















33

Active substance(s)

Trade


Tocilizumab

Ro-

actemra 2011










tide treatment






adults and children










Measles mumps













better medicines for children. from concept to reality

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