EMA 修订 PIP 合规核查与儿科奖励问答文件（EMA/PDCO/179892/2011 Rev. 3）
Questions and answers on the PIP compliance verification procedure at EMA, and on paediatric rewards
EMA 发布 PIP 合规核查与儿科奖励问答文件修订版 EMA/PDCO/179892/2011 Rev. 3，修订时间为 2026 年 10 月。文件说明上市许可申请、变更或扩展中的儿科验证与 PIP 合规核查流程，并列出第 36 至 38 条儿科奖励的适用条件。本轮更新主要涉及新的申报指南，其中第 24 节按修订后的 EMA 合规声明政策调整，第 25 节更新了相关问答链接。
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9 October 2026
EMA/PDCO/179892/2011 Rev. 3
Human Medicines Division
Questions and answers on the PIP compliance verification
procedure at EMA, and on paediatric rewards
(revised October 2026)
1. What is the purpose of this document?
The purpose is to explain to applicants the ‘paediatric validation’ of a marketing authorisation
application (MAA) / variation / extension of marketing authorisation, as well as a paediatric
investigation plan (PIP) compliance check. Information is also provided on the rewards foreseen by
the Paediatric Regulation.
2. What are the main changes compared to the previous
guidance document?
Updates relate to new submission guidelines.
3. What are the key reference documents?
This document should be read in conjunction with:
• Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal
products for paediatric use, as amended by Regulation (EC) No 1902/2006.
• European Commission — Guideline on the format and content of applications for agreement or
modification of a paediatric investigation plan and requests for waivers or deferrals and
concerning the operation of the compliance check and on criteria for assessing significant
studies;
• EudraLex Notice to applicants, volume 2B, Module 1 Administrative Information Application form;
• Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of
variations to the terms of marketing authorisations for medicinal products for human use and
veterinary medicinal products;
• Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009
concerning the supplementary protection certificate for medicinal products.
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Abbreviations/terms used in this document:
• Competent authority: The national competent authority (NCA) for products authorised via
the national, mutual recognition or decentralised procedure, and the European Medicines
Agency/European Commission for medicinal products using the centralised procedure.
• PIP: paediatric investigation plan.
• Paediatric Regulation: Regulation (EC) No 1901/2006, as amended by Regulation (EC) No
1902/2006.
• Regulatory application: for the scope of this document, a “regulatory application” is defined as
an application for a marketing authorisation, or an application for extension of marketing
authorisation, or a variation.
COMPLIANCE CHECK
4. What is a compliance check?
Compliance check is the verification that some or all studies/measures agreed in a PIP have been
conducted in accordance with the PIP decision, including compliance with the agreed timelines for
completion of measures.
5. What is the difference between a ‘full’ and ‘partial’
compliance check?
When the compliance check is performed for a fully-completed PIP, in other words on all measures,
this is referred to as a ‘compliance check on a PIP, fully completed’, or more briefly as a ‘full
compliance check’. A positive outcome of the full compliance check is one of several requisites for
obtaining the rewards or incentives described in Articles 36 to 38 of the Paediatric Regulation. A full
compliance check conducted by the Paediatric Committee (PDCO) results in a PDCO opinion, which is
final upon adoption. There is no re-examination procedure nor EMA decision for compliance checks.
At the time of submission of a regulatory application triggering the paediatric requirements, a full
compliance check may not be applicable, because the paediatric development programme is still
ongoing, and a deferral has been granted by the PDCO. A deferral may be granted for the initiation
and/or completion of one or more of the measures included in the PIP. In such cases, a ‘compliance
check on measures included in an agreed PIP, which are not deferred or due to be completed at the
time of a regulatory submission’, or more briefly, a ‘partial compliance check’, may be necessary.
The partial compliance check will cover all of those measures, within the condition(s) that cover the
therapeutic indication(s) included in the regulatory application, for which initiation and/or completion
have not been deferred, and also those measures which are deferred, but whose date of completion
occurs before the date of submission of the regulatory application.
6. What is a ‘paediatric validation’ and how is it different
from the compliance check?
For a regulatory application (as defined in Q&A 3) to be valid, it must include the documents
mentioned in Article 7 of the Paediatric Regulation; if these documents include a PIP decision, the
measures must be conducted in compliance with the EMA decision. The competent authority
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receiving the regulatory application will check that the requirements of the Paediatric Regulation
have been met as part of the overall validation of that application.
If all conditions for which one or more indications are being applied for are covered by a product-
specific waiver or a class-waiver decision, then no compliance check is required.
A full or partial compliance check (Q&A 4, 5) will be performed either: (i) prior to submission of the
regulatory application on request of the applicant, or (ii) at the validation stage of the regulatory
application, if no prior request to the PDCO has been made by the applicant.
If both the initiation and the completion of all the measures within the condition(s) (covering the
indication[s] in the application) have been deferred as detailed in the PIP decision, and none of the
dates of completion fall before the date of submission of the regulatory application, no compliance
check is required. If the initiation of a measure is not deferred, then a compliance check will only be
performed on the initiation of the measure.
7. Who performs the validation and the compliance check?
Applicants are strongly advised to submit compliance checks requests well in advance of any planned
regulatory application, whether centralised or non-centralised.
For centralised procedures, when a compliance check has not been requested from the PDCO in
advance, it will be performed as part of the regulatory application validation; EMA will either
perform it during the normal validation timelines, or may request the involvement of the PDCO
where appropriate. It should also be noted that, pursuant to Article 23(3) of the Paediatric
Regulation, the legally mandated timeframe for conducting a compliance check is 60 days. During
this period, the validation of the application may be suspended if necessary. Consequently, the
compliance check procedure may not be fully completed within the standard validation timeframe.
For applications following the national, mutual recognition or decentralised route, the national
competent authority(ies) will perform the validation; NCA(s) have the option to request that the
PDCO checks the compliance.
When compliance is checked by the PDCO ahead of the regulatory application submission, validation
will still need to be performed by the competent authority.
8. How early before submission of the regulatory application
can a compliance check be requested?
The Paediatric Regulation does not establish a timeframe for compliance checks prior to submission
of regulatory applications.
To prevent delays at the validation stage of a regulatory application, applicants are encouraged to
request compliance checks by the PDCO well in advance (i.e. at least 3 months) prior to the planned
submission of a regulatory application, in keeping with the submission timelines indicated on the
Paediatric medicines: applications and procedures webpage.
It is recommended that, when indicated, applicants submit separate sequential compliance check
applications to the PDCO, before submission of the regulatory application (centralised or non-
centralised). This is intended to confirm compliance of individual measures (or groups of measures) as
early as possible, on an ongoing basis, and to allow applicants more time if changes are needed. For
example, an applicant may submit one compliance check request after completing all the non-clinical
studies, and another after completion of the first clinical trial in children, before submitting their MAA
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in adults.
However, applicants should pay attention to the agreed timelines for completion of measures, which
need to be met on submission in all cases, i.e. those of measures which would need to be completed in
between an ‘early’ compliance check and the application submission date.
9. I am coming for a pre-submission meeting at EMA before
applying for a marketing authorisation (or other regulatory
application). Can I discuss a compliance check?
Yes, one of the aims of a pre-submission meeting is to ensure that an application can be validated.
During this meeting, the applicant may discuss:
• the Paediatric Regulation requirements;
• the need for compliance with the agreed PIP – if this is necessary, the applicant will be
encouraged to submit a compliance check request to the PDCO prior to submitting the
regulatory application (see Q&A 8, 10).
10. How do I apply to the PDCO for a compliance check?
Applicants may ask the PDCO to confirm compliance, in advance of their regulatory applications;
this can be done sequentially, in stages (see Q&A 8 above). Alternatively, applicants can choose to
submit their marketing authorisation (or other regulatory) application without having previously
obtained a compliance check; in this case, compliance will be checked as part of the validation
procedure (see also Q&A 7).
All information on the procedure, timelines, and the relevant forms, can be found on the following
webpage. For instructions on how to request a compliance check, please refer to the ‘Procedural
guidance on paediatric applications’ on the same page:
Paediatric medicines: applications and procedures
11. Because of difficulties in its implementation, our PIP is
no longer workable or appropriate, and one or more key
elements of the PIP would not be respected. What should we
do?
As non-compliance with the PIP will prevent validation of the regulatory application, the applicant
should consider submitting a request to the PDCO for modification of the agreed PIP, properly
justifying the deviations from the PIP. The PDCO will assess the requested changes and decide
whether they are justified.
Further information on the procedure for requesting modification of an agreed PIP can be found in
the ‘Procedural guidance on paediatric applications’, available on the webpage linked to above.
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12. The agreed PIP includes two (or more) conditions, but
the proposed indication of the next regulatory application is
only for one of them. Will compliance check be performed on
studies/measures for all conditions, or just for the condition
covered by the upcoming regulatory application?
For the purpose of validation, compliance with measures and timelines is checked only for the
condition(s) relative to the applied indication(s). This is a ‘partial’ compliance check if other conditions
are also covered by the PIP decision (Q&A 5). To benefit from the rewards and incentives of Articles
36-38 of the Paediatric Regulation, a full compliance check is necessary (Q&A 4).
13. My regulatory application includes a product-specific
waiver covering all subsets of the paediatric population. Can I
be sure that my regulatory application will be validated?
As there is no PIP, no compliance check is required. However, it is important to note that for a
waiver covering all subsets of the paediatric population, only indications included in the PIP
condition(s) specified in the EMA decision are covered. If, for example, a new indication is not
covered by the condition(s) of the waiver decision, a PIP or a waiver decision for this new condition
would be required.
14. I have a PIP without any deferral. What do I need to do?
All measures relating to the condition(s) covering the indication(s) proposed in the regulatory
application must be completed by the time of submission of the application. If a compliance check
has not been requested to the PDCO in advance, it will be performed during the validation of the
marketing authorisation application. To prevent delays at the validation stage, applicants are
encouraged to request compliance checks well in advance (i.e. at least 3 months) prior to the
planned submission of a regulatory application (see also Q&A 5 and 8 above)
15. I have a PIP with one or more measure(s) deferred.
What do I need to do?
Initiation and/or completion of measure(s) may be deferred. This means that an applicant can submit
a regulatory application for the condition(s) even if the deferred measures are either not initiated or
not completed (as relevant).
However, when one or more agreed measures are not deferred, or when the completion date
(timeline) of a measure falls earlier than the date of submission of the regulatory application (and
consequently the measure is due), then a partial compliance check is necessary (see also Q&A 5).
Also, please note that if a deferred measure is in fact completed and results are being submitted in
the regulatory application, a compliance check will have to be done on that measure, even if the
measure is not yet due.
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16. The validation procedure for my regulatory application
has determined that a compliance check is required. What
happens now?
For centralised procedures, if a compliance check needs to be done as part of the validation, EMA
will ask the applicant to provide the relevant additional information for the procedure, to be
submitted using the following template:
• Template - Request for compliance check on an agreed paediatric investigation plan (PIP)
For regulatory applications following non-centralised routes, the applicant may be requested to
submit relevant documents by the competent authority for processing validation. The competent
authority may request that the PDCO checks compliance (Q&A 7 and 8).
17. How long do validation and compliance check procedures
last?
The ‘paediatric’ validation is part of the overall validation of the application. It includes the
compliance check where necessary, and follows the validation timelines of the marketing
authorisation application, or of the variation/extension of marketing authorisation, respectively.
Validation may be suspended for up to 60 days to address compliance issues. EMA aims to provide
an outcome in the shortest possible time. The compliance check procedure has no clock stop,
therefore applicants should provide any requested clarifications as soon as possible (Q&A 8 and 10).
18. What is the compliance and validation procedure at NCA
level?
The NCA will assess the validity of the application using the same criteria as EMA/PDCO. NCAs can
either assess compliance themselves, or request a compliance check by the PDCO, in all cases before
completing validation. In the latter case, the NCA sends the compliance check request to EMA. Once
adopted, the PDCO letter, or opinion with compliance report, will be sent to the NCA.
19. What happens if the compliance check is negative?
If the compliance check is negative, the regulatory application cannot be validated.
If appropriate and justified, a request for modification of the agreed PIP could be submitted.
Provided the PDCO accepts the justification(s) and there is compliance with the latest EMA decision,
or a waiver is issued, the regulatory application may be subsequently validated.
20. What happens if, after an initially positive compliance
check, the subsequent assessment of my regulatory
application by the competent authority concludes that the
development was actually not performed in conformity with
the PIP decision?
In exceptional cases, after a positive compliance check by the PDCO, EMA or NCA, and successful
validation of the regulatory application, if the scientific assessment of the regulatory application
concludes that the paediatric development did not conform with the agreed PIP, the assessment will
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continue but the medicinal product will not be eligible to the paediatric rewards foreseen in Articles
36, 37 and 38.
21. Are outcomes of compliance checks published?
Outcomes of final compliance checks are published on EMA’s paediatric medicines webpages, next to
the relevant PIP decision. Information on final compliance checks are also reported in the Committee
for medicinal products for human use (CHMP) assessment report, and the European Public
Assessment Report (EPAR).
22. Are there other obligations for marketing authorisation
holders, regarding compliance with the agreed PIP?
Once a medicinal product is authorised, the marketing authorisation holder has to report annually
on all the deferred measures of the ongoing paediatric product development. Failure to comply with
this obligation will be reported to the competent authority (Article 34(4) of the Paediatric
Regulation).
Non-compliance with the EMA decision, or the reporting obligations, will be reported to the European
Commission as part of the public annual report referred to in Article 50 of the Paediatric Regulation.
REWARDS
23. What are the rewards foreseen in the Paediatric
Regulation?
If the requirements of the Paediatric Regulation are fulfilled (see below), applicants may benefit from
the following rewards:
• a six-month extension of the supplementary protection certificate (SPC), for the medicinal
products that are covered by an SPC or a patent qualifying for an SPC (Article 36);
• a two-year extension of the market exclusivity, for the medicinal products that are orphan-
designated (Article 37);
• a ten-year period of market protection, including an 8-year period of data exclusivity, in the
framework of a paediatric-use marketing authorization (PUMA), preventing generic applications
to rely on the dossier of the reference product or placing the product on the market.
Other incentives are also available for the development of medicinal products in children at EU or
national level, such as free scientific advice and protocol assistance at the Agency or funding. See also
the specific incentives for a PUMA application.
References
• Inventory of Community and Member State rewards and incentives
• Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal
products for paediatric use, as amended by Regulation (EC) No 1902/2006.
• Regulation (EC) No 469/2009.
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24. What are the conditions to be eligible for paediatric
rewards under Articles 36 and 37? 1
Medicinal products may be eligible for the rewards stated in Articles 36 or 37 of the Paediatric
Regulation, if all the following conditions are fulfilled:
• the applicant complied with all the measures contained in the agreed completed paediatric
investigation plan (PIP) and this is demonstrated in the application;
• the Summary of Product Characteristics, and if appropriate the Package Leaflet, reflects
the results of studies conducted in compliance with that agreed PIP;
• a statement indicating compliance of the application with the agreed PIP and including a
sentence that the PIP could be considered by the competent authorities for rewards, has
been included in the marketing authorisation;
• the medicinal product is authorised in all EU Member States.
As the rewards under Articles 36 or 37 are for conducting studies in the paediatric population, they
can be granted irrespective of the fact that the information generated in compliance with the agreed
PIP fails to lead to the authorisation of a paediatric indication.
Applications for an extension of the duration of an SPC already granted should be submitted to the
relevant national patent office(s) no later than two years before the expiry of the certificate.
Applicants are therefore encouraged to submit their application to reflect the results in the product
information and the inclusion of the compliance statement in the marketing authorisation sufficiently
in advance.
In case of granting of a new paediatric indication that leads to an additional period of market
protection under Article 14(11) of Regulation (EC) No 726/2004, this indication cannot also serve to
benefit from the paediatric reward as foreseen in Article 36(5) of Regulation (EC) No 1901/2006.
The rewards provided by the paediatric regulation for non-orphan medicinal products cannot be
cumulated.
For the reward stated in Article 37 of the paediatric regulation, the medicinal product needs to be an
orphan medicinal product benefiting from market exclusivity referred to in Article 8(1) of Regulation
(EC) No 141/2000.
The extension of market exclusivity for an orphan medicinal product can only be granted if the said
period of market exclusivity has not expired.
Applicants are therefore encouraged to submit their application to reflect the results in the product
information, and the inclusion of the compliance statement in the marketing authorisation, sufficiently
in advance of the expiry of the market exclusivity, taking into account the possible duration of
completing a Type-II variation or an extension to a marketing authorisation.
References
• Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal
products for paediatric use, as amended by Regulation (EC) No 1902/2006 and by
Regulation (EU) No 2019/5.
1
Section 24 has been amended in October 2026 to accommodate the Revised EMA Policy on Compliance Statement.
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• Regulation (EC) No 469/2009.
25. How are the results of measures performed in compliance
with an agreed PIP to be submitted? 2
Please see:
Q&A 24 type II variation - Type-II variations: questions and answers | European Medicines Agency
(europa.eu)
Q&A 18 line-extension - Extensions of marketing authorisations: questions and answers | European
Medicines Agency (europa.eu)
Q&A 3.2.1 pre-authorisation guidance - Extensions of marketing authorisations: questions and answers |
European Medicines Agency (europa.eu)
26. How is the compliance statement with an agreed
completed paediatric investigation plan issued, and
published, for centrally authorised medicinal products?
Article 28(3) of the Paediatric Regulation states: “If the application complies with all the
measures contained in the agreed completed paediatric investigation plan and if the
summary of product characteristics reflects the results of studies conducted in
compliance with that agreed paediatric investigation plan, the competent authority shall
include within the marketing authorisation a statement indicating compliance of the
application with the agreed completed paediatric investigation plan.”
If the application is for marketing authorisation, the compliance statement is included in the
Commission Decision. Decisions granting marketing authorisation are published on the Community
Register of medicinal products for human use.
Since 2 November 2012, if the application is for varying the terms of an existing marketing
authorisation, the compliance statement will be included in the technical dossier of the marketing
authorisation. Therefore, when the opinion is adopted by the CHMP, EMA provides the marketing
authorisation holder with confirmation that the statement is included in the technical dossier by
means of an annex to the cover letter of the opinion.
This annex is also published in the product webpage of the medicinal product ('Find medicine - Human
medicines – EPAR - Assessment history').
References
• Regulation (EC) No 1901/2006 of the European Parliament and of the Council on medicinal
products for paediatric use, as amended by Regulation (EC) No 1902/2006.
• Regulation (EC) No 1234/2008.
27. How do I know if a medicinal product was granted an
extension of the duration of the Supplementary Protection
2
Section 25 has been amended with up-to-date links to Q&A.
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Certificate?
Companies are invited to liaise with the relevant national patent offices for any questions related to
the extension of the duration of the SPC covering their medicinal product.
28. How do I know if an orphan medicinal product was
granted an extension of the duration of the market
exclusivity?
Orphan medicinal products to which the extension was granted will contain a statement in the body
of the relevant Commission Decision, mentioning the extension of the duration of the market
exclusivity: “The market exclusivity period referred to in Article 8(1) of Regulation (EC) No 141/2000
is extended to twelve years in accordance with Article 37 of Regulation (EC) No 1901/2006.” This
could be either part of the initial marketing authorisation or a subsequent variation. Commission
Decisions are published on the Community Register of orphan medicinal products for human use.
Those products will be maintained in the Community Register of orphan medicinal products for an
additional period of two years.
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