The EU
Paediatric
Regulation:
Operational and Strategic
Considerations
(Industry Perspective)
By Neil Edwards
N
ew legislation, Regulation (EC) No
1901/20061, 2 (the Paediatric Regulation),
governing the development and regulatory approval of medicines in children became effective in Europe in January 2007. The Paediatric
Regulation imposes significant obligations on the
pharmaceutical industry to address the potential
need for paediatric development as a prerequisite
for approval in the adult population. In return,
companies are offered incentives for addressing the
challenge of pharmaceutical development in the
paediatric population. The regulation applies to all
medicinal products for human use except generic
products, biosimilar products, products authorised
by well-established use, and homeopathic and
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March 2008
traditional herbal medicines. While the regulation
entered into force in January 2007, transitional
provisions apply, i.e., the paediatric obligation
applies to new medicines not previously approved
in the EU from 26 July 2008, and to line extensions of authorised on-patent medicines from 26
January 2009.
With the advent of the Paediatric Regulation,
it is critical that all companies active in European
product development and regulatory approval
evaluate the legislation’s impact. To fully assess the
potential impact, companies must consider the
status of existing intellectual property protection,
established product development plans and regulatory strategies together with lifecycle management
and line extension strategies.
The US has a well-developed, evolving regulatory system to encourage the development of
medicines in the paediatric population.3 However,
the new EU paediatric requirements differ in a
number of important respects from that system.
In Europe, it is generally necessary for a paediatric development plan to be formally agreed upon
with the authorities at an earlier stage than in the
US. Additionally, the EU procedures for reaching
agreement on the development plan tend to be
more formalised.
The Paediatric Regulation redefines Europe’s
drug development process by requiring companies
to formally agree upon a paediatric development
plan with the regulatory authorities at the end
of phase 1 in adults. Consequently, the development of a medicine in the paediatric population
must now be considered in parallel with adult
development. The regulation’s impact is profound,
significantly increasing the regulatory authorities’
influence on the paediatric drug development
process with regard to the development plan’s content and timelines. This increased regulatory influence is exercised via the paediatric investigation
plan (PIP). The PIP is a research and development
programme aimed at ensuring that necessary data
are generated to determine the conditions under
which a medicinal product may be authorised to
treat the paediatric population. The Paediatric
Regulatory Focus
9
Table 1. Application Format for PIPs, Deferrals and Waivers
PART A
ADMINISTRATIVE AND PRODUCT INFORMATION
OVERALL DEVELOPMENT OF THE MEDICINAL PRODUCT INCLUDING INFORMATION
ON THE TARGET DISEASES/ CONDITIONS
B1: Anticipated similarities and differences in disease/condition
PART B
B2: Anticipated similarities and differences of effect of product on disease/condition
B3: Prevalence/incidence in paediatric population
B4: Current methods of diagnosis, prevention or treatment in paediatric populations
B5: Significant therapeutic benefit/fulfilment of therapeutic need
PART C
APPLICATIONS FOR PRODUCT-SPECIFIC WAIVERS
PAEDIATRIC INVESTIGATION PLAN
D1: Overall strategy proposed by the applicant for paediatric development
D2: Strategy in relation to quality aspects
D3: Strategy in relation to nonclinical aspects
PART D
D4: Strategy in relation to clinical aspects
D5: Planned measures for paediatric development
D5.1: Overall summary table for all nonclinical and clinical studies
D5.2: Outline of each planned/performed study/step in pharmaceutical development
D5.3: Synopsis/outline protocol of each planned/performed nonclinical study
D5.4: Synopsis/outline protocol of each planned/performed clinical study
D6: TIMELINE OF MEASURES IN THE PAEDIATRIC INVESTIGATION PLAN
PART E
APPLICATIONS FOR DEFERRALS
PART F
ANNEXES
Published literature, investigator brochure, scientific advice (including from third countries), latest approved
product information (SmPC, PIL, labelling) for an approved product.
Regulation requires that development in children must not delay Marketing Authorisation
in adults. In such cases, the timing of initiation
or completion of studies detailed within the PIP
may be deferred. The regulation also requires that
no unnecessary clinical trials are conducted in
children and provides the possibility of waiving
the need for a PIP.
A new committee established within EMEA,
the Paediatric Committee (PDCO), is central
to the new paediatric regulatory system. The
PDCO is responsible for approving, refusing or
requesting modifications of PIPs. It consists of
33 members: one representative from each of the
27 EU Member States plus representatives of six
stakeholder groups, three healthcare professional
organizations and three patient associations. The
PDCO currently is operating with the 27 EU
Member State representatives; the process of identifying the stakeholder representatives is ongoing.
The Paediatric Investigation Plan
The PIP details the studies and timing proposed to
investigate a medicine’s quality, safety and efficacy
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in the paediatric population. It must also describe
any measures required to adapt the formulation
to optimise it for use in the paediatric population.
Under the Paediatric Regulation, a PIP, deferral or
waiver must be submitted and agreed upon no
later than the completion of adult pharmacokinetic studies. This ensures that an opinion on the
medicine’s use in the paediatric population can be
given at the time of the Marketing Authorisation
Application (MAA) assessment, unless a waiver or
deferral has been granted.
For products within the scope of the Paediatric
Regulation, an MAA will only be considered valid if
it includes the results of studies performed in compliance with an accepted PIP, or a decision granting
a waiver or deferral. For new medicines not previously authorised in the EU, this requirement applies
from 26 July 2008. For line extensions of authorised
medicines protected by a supplementary protection
certificate (SPC) or qualifying patent, the requirement is applicable from 26 January 2009. A line
extension is defined as a new indication, new pharmaceutical form or new route of administration.
For line extensions, the PIP must cover the existing
and the new indication, pharmaceutical form and
route of administration, unless a waiver is appropriate for the existing authorised particulars.
The regulation defines the paediatric population as covering the ages from birth up to (not
including) 18 years of age. The paediatric population is not considered to be one homogeneous
group and, therefore, the PIP must address all
individual subsets per ICH Guideline E11, i.e.,
pre-term/term neonate (aged 0 to 27 days), infant
(aged 1 to 23 months), child (aged 2 to 11 years)
and adolescent (aged 12 to, but not including, 18
years). In some instances, it is likely the PDCO
will agree that the use of ICH paediatric subsets
may not be optimal, with alternative subsets
being appropriate. However, when a company
considers an alternative stratification of the paediatric population appropriate, this must be fully
justified in the PIP with a convincing rationale to
support the alternative approach.
The PDCO is responsible for considering
the proposed methodology and expected therapeutic benefit of the medicine’s paediatric use
both in clinical trials and under a Marketing
Authorisation. A waiver may be granted in
those cases where no benefit is expected, to
avoid unnecessary clinical trials in children.
Alternatively, the PDCO may grant a deferral
where more data are considered necessary before
undertaking paediatric studies, to avoid delaying a
Marketing Authorisation in adults. Where appropriate, it may grant a partial waiver or deferral
applicable only to a specific subset of the paediatric population.
Applications for PIPs,
Deferrals and Waivers
Guidance on PIP application format and content
is provided in a European Commission draft
guideline,4 which is currently under public consultation. The final guideline is expected to be
identical in most important aspects to the draft.
Applications for PIPs, waivers or deferrals must
all follow the format defined in the Commission
Guideline. This format is summarised in Table 1.
Part B5 (Significant therapeutic benefit/
fulfilment of therapeutic need) is a key section
of the PIP. Central to the PDCO decision on
giving a PIP a positive opinion or granting a
waiver is whether the product’s use in children
during marketing or in clinical trials is expected
to be of significant therapeutic benefit or fulfil
a therapeutic need. To persuade the PDCO
that the applicant’s position is appropriate, it is
important to provide a convincing and justified
rationale for significant therapeutic benefit.
Possible justification for claiming significant
paediatric therapeutic benefit include:
• expected improved efficacy compared to
current standard of care
• expected substantial improvement
in safety relative to adverse events or
potential medication errors
• improved dosing scheme or method
of administration leading to improved
efficacy, safety or compliance
• different mechanism of action with
potential efficacy or safety advantages
Since experience with a medicine’s use in the paediatric population might be unavailable or very
limited at an early stage of development, significant therapeutic benefit can be based upon welljustified and plausible assumptions, If significant
therapeutic benefit cannot be fully justified at an
early development stage, the PDCO may grant
a waiver or deferral. If the indication is included
in the EU inventory of therapeutic needs,5 this
should be referenced within Part B5 of the PIP.
Where the indication is not included in the
inventory of therapeutic needs, it is important
that the applicant provide sufficient information
to justify the claimed therapeutic need.
Part D of the PIP discusses the paediatric
development strategy, including details of
studies to be completed and timelines for their
completion. Topics for discussion regarding quality
aspects (Part D2) include suitability of existing
pharmaceutical forms, the need for specific
formulations or dosage forms relative to the chosen
age group(s), the chosen formulation/dosage
form’s benefit, the development timeframe for
age-appropriate dosage form and potential issues
in relation to formulation, e.g., appropriateness
of excipients. For intravenous products,
it is important to adequately address the
potential need for reformulation to provide an
appropriate dosage strength and administration
volume/regimen for paediatric use. In Part D3,
nonclinical aspects for consideration include
the need for additional nonclinical development
beyond standard or existing data, e.g., the need
for studies to address specific toxicity endpoints
at a developmental phase. Clinical aspects to be
discussed in Part D4 include:
• overall clinical approach to support
development in the PIP indications and
paediatric age subsets
• rationale to support dosing and route of
administration
Regulatory Focus
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Table 2. List of Conditions Subject to Class Waiver
Treatment of conditions subject to class waiver of PIP requirement
Oropharyngeal Carcinoma (excluding Nasopharyngeal)
Lung Carcinoma (Small Cell and Non-small Cell Carcinoma)
Basal Cell Carcinoma
Breast Carcinoma
Ovarian Carcinoma (excluding Rhabdomyosarcoma and Germ Cell Carcinoma)
Endometrial Carcinoma
Prostate Carcinoma
Hairy Cell Leukaemia
Multiple Myeloma
Alzheimer’s Disease
Vascular Dementia and Vascular Cognitive Disorder/Impairment
Organic Amnesic Syndrome (excluding amnesic syndrome caused by alcohol/other psychoactive substances)
Amyotrophic Lateral Sclerosis
Parkinson’s Disease (non-juvenile)
Age-related Macular Degeneration
Menopausal and Other Perimenopausal Disorders
COPD (with exclusions)
•
•
•
•
justification of the choice of subjects,
being representative of the intended
treatment population
need for specific dose finding studies, ageappropriate endpoints and efficacy data
need for safety data and potential risks
by age groups
feasibility of proposed studies, e.g.,
potential recruitment issues
PIP Part D5 includes overall summary tables of
the proposed nonclinical and clinical studies,
with an outline of each planned or performed
study/step in the pharmaceutical development.
Synopses/outlines must be provided for each
planned or performed nonclinical study, including details of the study type and objective, test
system/species, method of administration and
duration of dosing. A synopsis/outline of each
planned or performed clinical study must also be
provided, including the following:
• study design
• type of control: placebo or active
(including dose)
• location (regions)
• test product: dosage regimen, duration
and route of administration
• study objective
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March 2008
•
•
•
•
•
•
•
umber of subjects: male/female, ages,
n
number per ICH or alternative relevant
age group
main inclusion/exclusion criteria
endpoints: primary and secondary
sample size
power calculation: including description of effect size
option in case of recruitment issues: interim
analysis and early close of study rules
statistical methods
Study timelines must be discussed in PIP Part D6,
including specific dates for each study’s initiation,
completion, analysis and reporting. Once the PIP
has been accepted by the PDCO, any changes
proposed by the applicant must be submitted for
PDCO approval. When conducting a paediatric
development programme, a number of iterative PIP modifications may be required to adjust
agreed-upon methodologies and timelines. It is,
therefore, important that information in the PIP
regarding study timelines and methodology be sufficiently robust to minimise the need for repeated
PIP amendments. When drafting a PIP, an appropriate balance must be struck in the level of detail
provided. It must provide sufficient information
for PDCO assessment, but should avoid excessive
detail to simplify subsequent change management.
Applications for PIP modification follow the same
structure for Part D as an initial PIP application,
with only those sections relevant to supporting the
change completed.
Application for Deferral
The Paediatric Regulation allows the initiation or
completion of measures/studies detailed within a
PIP to be deferred. The request for deferral must
be made at the time of initial PIP submission.
The request must justify the indication, route of
administration and pharmaceutical form and the
specific age group to which the deferral applies.
Justification must be on scientific and technical or public health-related grounds. Possible
grounds for deferral include:
• appropriate efficacy studies must be
conducted in adults prior to initiating
paediatric studies
• studies in the paediatric population take
longer than in adults
• additional nonclinical data are required
before starting paediatric studies
• quality problems delay development of
appropriate formulations
When a deferral is granted, following Marketing
Authorisation (MA) approval the MA holder is
required to submit an annual report to EMEA
updating progress on the deferred studies.
Application for Waiver
Waivers may be granted for one or more paediatric subsets, one or more specified indications
or a combination of both. Absence of available
safety and efficacy data will not be accepted as
the only justification for a waiver. Requests for
product-specific waivers must define the scope of
the paediatric subset and the indication for which
the waiver is requested, and must also specify the
pharmaceutical form and route of administration. Product-specific waivers may be granted for
efficacy and safety grounds. Possible justifications
include effects observed in nonclinical and, when
available, clinical studies, or established inefficacy
for products of the same class. Other grounds for
product-specific waivers are occurrence of the disease/condition in adults only, and a lack of significant therapeutic benefit. It is possible for a PIP
waiver to be revoked; in such cases, the applicant
must agree a PIP with the PDCO within 36
months of the waiver revocation date.
In December 2007, EMEA adopted a list of
conditions that occur only in adult populations.
Medicines to treat these conditions are subject
to a class waiver and are exempt from the PIP
requirement for all paediatric population subsets.6
However, even where a class waiver exists, the
applicant must still apply to the PDCO for a
product-specific waiver since this decision is
required for MAA validation. Table 2 lists the
conditions to which a class waiver applies.
Paediatric Procedure
Whether the application is for a PIP, a waiver or
a deferral, the same procedure is followed. EMEA
has published guidance on the practical aspects of
submitting PIP applications,7 and EMEA’s template must be used to prepare the applications.8
The template includes sections for administrative
information corresponding to Part A of the PIP,
with the information corresponding to Parts B to
F being appended to it. An applicant must notify
EMEA of its intention to submit a PIP, usually
three months in advance, using a standard letter of
intent.9 Applications must be submitted in line with
published submission dates based upon the PDCO
meeting schedule.10, 11 A PIP assessment is led by a
Rapporteur and peer reviewer, both of whom are
appointed from within the PDCO. The procedure
for PIP agreement is presented in Table 3. The
paediatric procedure allows several opportunities for
discussions between applicant and the PDCO.
Within 10 days of the PDCO opinion,
EMEA communicates it to the applicant. The
PDCO opinion then becomes final unless the
applicant requests re-examination of it. Such
requests for re-examination must be made within
30 days of the PDCO opinion. If such a request
is received, a new Rapporteur is appointed to
lead the reassessment. The final PDCO opinion
is given within 30 days of receipt of the appeal.
The EMEA decision is adopted within 10 days of
the final PDCO opinion.
Compliance Checks
When the PDCO has agreed to a PIP, the
Paediatric Regulation requires that the company
follow the PIP exactly. Once the PIP is completed,
during validation of the MAA the authorities are
required to confirm that the company has complied with all studies, measures and timelines in
the PIP. For Centralised Procedure applications,
EMEA conducts this PIP compliance check;
for Decentralised Procedures (DCP) or Mutual
Recognition Procedures (MRP), the Reference
Member State (RMS) is responsible for the compliance check. This compliance check is required
before an MA application can be considered valid.
Regulatory Focus
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Table 3. Paediatric Procedure
Day
Procedural Step
Day -30
Submission of application to EMEA for validation
Day 0
Day 30
Day 60
Validation of application by EMEA
(summary report to PDCO)
or
Request for supplementary information from applicant (clock stop)
Submission of requested information by applicant
First PDCO discussion
Second PDCO discussion (possible meeting with applicant)
Adopt positive opinion (PIP agreement, waiver or deferral)
or
Request modification of PIP (list of issues to applicant)
Clock Stop: (up to 3 months)
Day 61
Submission of applicant’s response and clock start
Day 90
Third PDCO discussion
Day 120
Fourth PDCO discussion (possible meeting with applicant)
Adopt positive opinion (PIP agreement, waiver or deferral)
The PDCO may be asked to give an opinion on
whether the applicant’s studies are in compliance with the PIP. This PDCO opinion can be
requested by the applicant prior to MAA submission. Alternatively PDCO opinion may be
requested by the relevant authority:
• when validating the MAA, if the
application does not already include a
PDCO opinion on PIP compliance.
For Centralised Procedure applications,
this request is made by EMEA; for
DCP and MRP, the PDCO opinion is
requested by the RMS.
• during MAA assessment, when there
is doubt concerning compliance and a
PDCO opinion has not been previously
requested. For Centralised Procedure
applications, such a request for a PDCO
opinion is made by CHMP; for DCP and
MRP, the request is made by the RMS.
In addition to giving an opinion regarding PIP
compliance, the Rapporteur or RMS can ask the
PDCO to assess data generated in accordance with
a PIP during the regulatory review of an MAA and
to formulate an opinion on the medicine’s quality,
safety and efficacy for use in children.
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Incentives for Compliance With the
Paediatric Regulation
The Paediatric Regulation provides specific intellectual property and regulatory incentives to companies
for developing and marketing paediatric medicines.
The intellectual property rewards are a six-month
SPC extension for new medicines not previously
authorised in Europe, and line extensions of authorised medicinal products protected by an SPC
or qualifying patent. To maximise potential SPC
extension benefits, companies must fully consider
all available options and strategies for protection of
their intellectual property. Consideration should be
given to the potential benefits of applying for an
SPC, even if less than five years has elapsed between
patent filing and MA approval, to benefit from the
six-month SPC extension.12 Orphan drugs benefit
from a two-year market exclusivity extension, from
10 years to 12. Table 4 details the requirements
that must be fulfilled to obtain the regulation’s
intellectual property rewards.
Regulatory incentives include applications for
PIP agreement, modification, waiver, deferral and
compliance check at no charge. Application fees
for requests for CHMP Scientific Advice relating to paediatric development of medicines are
also waived. However, where a mixed request for
scientific advice relating to adult and paediatric
development issues is submitted, the fee waiver
only applies to the request’s paediatric aspects, i.e.,
normal fees apply for scientific advice requested on
aspects relating to development in adults.
When a deferral is granted, the rewards
offered under the Paediatric Regulation are available only when all deferred studies are completed,
thereby encouraging companies to complete them
as quickly as possible. However, the SPC must
still be valid when the deferred studies are completed for the company to benefit. Incentives are
not available if a class waiver or product-specific
waiver has been granted.
Paediatric Use Marketing
Authorisations
To encourage companies to conduct paediatric
development with off-patent medicines, the
Paediatric Regulation establishes the Paediatric
Use Marketing Authorisation (PUMA). The
nonclinical and clinical data contained within a
PUMA receive 10 years of data protection/market
exclusivity. PUMAs also benefit from optional
access to the Centralised Procedure, with a reduction in the normal application fees. A medicine
approved via a PUMA can maintain the same
trade name as the original product for adults if
the applicant is the original MAH. This enables
holders to benefit from the heritage of the originator MA brand.
With the exception of PUMAs, positive
paediatric data are not a prerequisite for receiving
the intellectual property rewards, i.e., the reward
is granted for completing paediatric development and generating helpful information on the
medicine’s use in children, regardless of whether
the drug is found to be safe or effective in the
paediatric population. In the case of a PUMA,
positive data are required since the Marketing
Authorisation to which data protection and market exclusivity apply cannot be granted without
positive efficacy and safety data.
Other Factors for Consideration
The Paediatric Regulation required MA holders to
submit all paediatric studies completed by the date
of entry into force of the legislation (26 January
2007) to regulatory authorities by 28 January
2008. In addition, there is an ongoing requirement that all MAH-sponsored paediatric studies
with any authorised medicine be submitted to the
authorities within six months of their completion.
Any company that has benefited from a
paediatric reward must continue to market the
medicine after the extended market protection
expires. If an MAH intends to cease marketing, it
must either transfer the MA to another company
or consent to third-party applications for MA via
full cross-reference to quality, safety and efficacy
data. A company intending to cease marketing
a medicine that has benefited from paediatric
rewards must inform EMEA of this intention six
months in advance. EMEA then publishes the
names of the MA holder and the medicinal product to inform interested companies that may wish
to make third-party applications for MA.
The regulation requires product labelling for
any medicine granted MA for a paediatric indication to carry a symbol identifying it as a medicine
approved for paediatric use. The product’s patient
information leaflet must also include an explanation of the symbol. Selection of this symbol is currently ongoing. This symbol will be required to be
applied retrospectively to all medicines in Europe
already authorised for paediatric use. Once the
symbol is selected, companies will have two years
to apply it to existing paediatric medicines.
At EMEA’s request, the European
Commission (EC) has the authority to impose
financial penalties on companies for infringement
of the Paediatric Regulation. The EC will publish
the names of any company subject to such financial penalties, including the reasons and the scale
of financial penalties imposed.
Strategic Considerations
The Paediatric Regulation redefines the drug
development process in Europe by requiring companies to prospectively agree with the regulatory
authorities on the adequacy of proposed studies
to generate relevant quality, safety and efficacy
information. Development of a medicine in the
paediatric population must now be considered
in parallel with development in adults, with a
PIP required at the end of adult phase 1 studies. When preparing development plans for new
medicines and line extensions for on-patent medicines, it is important to give full consideration to
paediatric development and to identify the appropriate strategy—full PIP, deferral or waiver—and
elaborate it as the paediatric development plan.
The regulation increases the influence of
the regulatory authorities on the paediatric drug
development process with regard to development
plan content and timelines, with these details
requiring agreement prior to study initiation.
Therefore, it is important that study timeline
and methodology details in the PIP be robust to
reduce the need for repeatedly amending the PIP.
Regulatory Focus
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Table 4. Requirements for Granting Paediatric Reward
Paediatric studies completed in compliance with PDCO-agreed PIP
PIP compliance mentioned/confirmed in the MAA
Significant studies in the PIP completed after 26 January 2007
Results of paediatric studies (positive or negative) included in the Summary of Product Characteristics (SmPC)
and patient information leaflet (PIL)
Medicine authorised in all EU Member States
SPC not previously extended, i.e., must not benefit from +1 year additional marketing exclusivity on grounds
that new paediatric indication brings significant clinical benefit in comparison to existing therapies
Request for SPC extension filed at least two years prior to patent expiry. Until 2012, during a five-year transition
period, the request for SPC extension must be filed at least six months prior to patent expiry.
An appropriate balance must be struck in the
PIP, providing sufficient information to support
PDCO assessment but avoiding excessive detail
that could complicate subsequent change management. When conducting studies and creating
development plans in the paediatric population,
companies must consider the requirements and
time involved for PDCO agreement to PIP modifications implementing changes.
To prepare PIPs that address regulatory
expectations and are likely to receive PDCO
approval, companies should consider requesting
CHMP Scientific Advice to obtain regulatory
authority input into, and validation of, the proposed development plan. Full consideration must
be given to including ongoing studies in the PIP
and, if a company has a paediatric development
plan in the US, it should consider how best to
incorporate that information in the EU PIP. It is
particularly important that companies consider
the possibility of a joint, or global, paediatric
development plan for the EU and US given the
level of active cooperation and communication
between FDA and EMEA on issues relating to
paediatric drug development.
Designing and conducting clinical trials in
the paediatric population are challenging from a
number of perspectives, both practical and ethical.
The paediatric procedure is an additional regulatory
negotiation/approval process to be managed effectively alongside the existing regulatory prerequisites
for running clinical trials, i.e., ethics committee
approvals and clinical trial authorisations. Once the
PIP is agreed by the PDCO, regulatory approval
of clinical trial authorisations and ethics committee approvals are needed prior to study initiation.
Importantly, ethics committees and regulatory
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March 2008
authorities that approve clinical trials are not mandated to follow a PIP agreed upon by the PDCO.
Clinical trial authorisation and ethics committee
approval operate independently from the PIP procedures. Companies should anticipate requests for
changes to study design or for the submission of
additional nonclinical or clinical data from ethics
committees or regulatory authorities during clinical trial approval. Such a request would necessitate
PDCO approval of a modification to the PIP.
Therefore, it is more important than ever for pharmaceutical companies to fully align drug development, clinical research and regulatory processes.
Conclusion
It is critical for companies active in product
development and regulatory approval in Europe
to evaluate the effect of the new Paediatric
Regulation on their development projects. To
assess the potential impact, companies must consider the status of existing intellectual property
protection, product development plans, regulatory strategies and lifecycle management/line
extension strategies.
The Paediatric Regulation has a profound
impact for everyone involved in drug development and regulatory affairs in the EU. A proactive
approach in assessing the regulation’s effect on
each individual development plan and regulatory
strategy is important to ensure new regulatory
requirements are appropriately addressed. Whether
full PIP compliance, deferral or waiver is appropriate, timely identification of the optimal company
strategy to comply with the regulation is critical in
the evolving regulatory environment. Companies
should take a proactive approach to ensure compliance and avoid unnecessary issues or delays in
the drug development process under the new EU
Paediatric Regulation.
F
REFERENCES
1. Regulation (EC) No 1901/2006 of the European
Parliament and of the Council of 12 December 2006 on
medicinal products for paediatric use.
2. Regulation (EC) No 1902/2006—an amending regulation
in which changes to the original text were introduced
relating to decision procedures for the European
Commission.
3. Charlish P. “Clinical trials in paediatric populations.”
RAJ Pharma; July 2007; 465–469.
4. European Commission guideline on format and content
of applications for paediatric investigation plans.
5. EU inventory of paediatric needs (as established by
Paediatric Working party). Available at www.emea.
europa.eu/htms/human/paediatrics/inventory.htm.
6. European Medicines Agency decision of 3 December
2007 on a class waiver on conditions in accordance with
regulation (EC) 1901/2006.
7. “Practical aspects on how to submit an application for
paediatric investigation plan and requests for waiver and
deferral Rev. 5.” Updated 1 October 2007. Available
at www.emea.europa.eu/pdfs/human/paediatrics/practical_aspects.pdf.
8. Electronic template for PIP applications (Article 7,
Article 8, Article 30). Updated 17 August 2007.
Available at http://www.emea.europa.eu/pdfs/human/pae-
diatrics/PIP-application-form.pdf.
EMEA Template for letter of intent Rev. 1. Updated 1
October 2007.
10. PDCO meeting dates and timelines for submission of
applications—2008 Rev. 1. Updated 1 October 2007.
11. PDCO meeting dates and timelines for submission of
applications—2009. Published 1 October 2007.
12. Snodin M and Miles J. “Making the most of paediatric
SPC extensions.” RAJ Pharma; July 2007; 459–463.
9.
AUTHOR
Neil Edwards is Managing Director of Sirius Regulatory
Consulting Ltd., a progressive regulatory affairs consultancy
working with the global pharmaceutical industry to achieve
drug development and regulatory approval in the EU. He is
currently assisting a number of companies in addressing the
challenges of the EU Paediatric Regulation.
Visit www.siriusregulatory.com.
Regulatory Focus
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