Instructions are available on our ‘Paediatric applications and procedures’ webpage:
No, applicants and / or authorised contacts can be based anywhere. For further information (section 2.2.1):
No, a letter of intent is no longer required for paediatric applications.
For a medicinal products with multiple marketing authorisations (MAs) or future or ongoing marketing authorisation applications (MAAs), a single PIP decision can be used, provided that the marketing authorisation holder (MAH) or applicant are considered the same according to the Commission communication on the Community marketing authorisation procedures for medicinal products (98/C 299/03) ('Will Article 7 or Article 8 of the Paediatric Regulation apply to my application, taking into account the global marketing authorisation concept?').
Therefore, a single PIP application or a request for a waiver can be submitted to cover all of the marketing authorisations and applications for the medicinal product concerned.
It is recommended that there is only one single PIP or waiver applicant identified for the submission of the application.
This applicant will be the addressee of the Agency's decision; however, an appropriate PIP or waiver Decision can be used by an applicant who is not the PIP addressee, to satisfy the requirements of Article 7 or Article 8.
Before contacting EMA's Paediatric Medicines Office with your question(s), please first consult the questions and answers on this page, as well as the comprehensive information available under Paediatric medicines: applications and procedures: Procedural advice on paediatric applications.
To contact EMA's Paediatric Medicines Office, see Paediatric medicines: Research and development: Contact points.
Applicants who want to submit a paediatric application must have an RPI for their product, which can be requested via EMA's IRIS system, following the IRIS guide to registration, substances and RPIs:
If you cannot see an existing RPI in the list available when drafting a new submission, the most likely cause is that the RPI is assigned to a different organisation, for which you do not have an affiliation as IRIS Industry Manager, or to another individual. Please bear in mind that the organisation could be a different legal entity of the same multinational company.
To be able to visualise and select the RPI in a new submission, you have two possibilities:
Applicants can request scientific advice from EMA in preparation of a PIP, which is free of charge for questions relating to the development of paediatric medicines. They can also follow up a PIP with scientific advice, for example on combined adult and paediatric development in light of the PIP requirements.
EMA discourages applicants from submitting scientific advice and PIP applications in parallel.
Specific scientific questions on various aspects of paediatric development, including juvenile animal study design or paediatric formulations continue to be well within the scientific advice (SA) scope. In fact, most scientific questions remain within the remit of SA. The only questions the Scientific Advice Working Party does not address are those that fall under EMA' Paediatric Committee (PDCO) remit, such as:
In essence, the PDCO bears overall responsibility for agreeing, modifying or refusing a paediatric investigation plan. When designing a PIP, however, scientific advice may be requested about specific elements of it (but not about the plan as a whole), whereas paediatric pre-submission interactions assist in practical and regulatory aspects.
Comprehensive information on requesting scientific advice is available:
To contact the Paediatric Medicines Office about a pre-submission interaction, please consult our ‘Procedural advice on paediatric procedures’:
EMA is running a pilot for a 'stepwise PIP' agreement which would introduce a partial development programme supporting the authorisation of innovative medicines for children.
This programme would be conditional on the development of a full PIP once sufficient evidence becomes available. It would rely on predefined steps agreed with the EMA's Paediatric Committee (PDCO), such as applicants being able to hold discussions with the PDCO once they obtain more data.
Guidance on the stepwise PIP pilot is available below:
A stepwise PIP would apply to cases where there is a lack of crucial information needed to decide on certain parts of the paediatric investigation plan, such as whether a clinical study for a whole age group is necessary.
EMA launched this pilot in February 2023. It is due for review upon the adoption of eight initial opinions on stepwise PIPs.
Guidance on COVID-19 medicines is available for medicine developers and companies:
Joint procedural information is available from EMA and the United States Food and Drug Administration (FDA) for medicine developers submitting a paediatric investigation plan (PIP) to EMA and an initial paediatric study plan (iPSP) to the FDA.
This joint document aims to make it easier for developers to submit paediatric development plans simultaneously to the regulators, to help speed up the development and approval of COVID-19 treatments and vaccines:
The guidance in this section was intended for use during the COVID-19 public health emergency.
Given the rarity of childhood cancers, this joint guidance aims to speed up the development and authorisation of cancer medicines for children. It describes the information the two regulators typically require for their evaluations to support:
Please visit the IRIS forums for a variety of topics, including the communication to industry on data reconciliation relating to decisions on PIPs and product-specific waivers:
Applications for a marketing authorisation in respect of a medicinal product for human use which is not authorised in the European Union at the time of entry into force of Regulation (EC) No 1901/2006 have to comply with the requirements of Article 7 of Regulation (EC) No 1901/2006.
In accordance with Article 8 of Regulation (EC) No 1901/2006, the requirements of Article 7 shall also be applicable to the authorisation of new indications, new pharmaceutical forms or new routes of administration of authorised medicinal products which are protected by a supplementary protection certificate or by a patent which qualifies for the granting of a supplementary protection certificate.
Since Articles 7 and 8 refer respectively to 'a medicinal product for human use which is not authorised in the Community' and to an 'authorised medicinal product', at the time of submitting a new stand-alone application, it is necessary to establish whether the product applied for is considered or not a 'medicinal product for human use which is not authorised in the Community'. In this context, the global marketing authorisation concept, as defined in Article 6(1), 2nd subparagraph of Directive 2001/83/EC applies.
The global marketing authorisation includes the initial authorisation and all variations and extensions thereof, as well as any additional strengths, pharmaceutical forms, administration routes or presentations authorised, through separate procedures and under a different name, granted to the marketing authorisation holder of the initial authorisation. For further reference, see the notice to applicants, chapter 1, section 2.3. Thus, the global marketing authorisation concept applies to products belonging to the same marketing authorisation holder: according to the Commission communication on the Community marketing authorisation procedures for medicinal products (98/C 299/03), applicants belonging to the same mother company or group of companies, or which are 'licensees', have to be considered as one.
The global marketing authorisation (GMA) concept, together with the notion of 'same marketing authorisation holder', is used to determine whether an application concerns a 'medicinal product for human use which is authorised or not in the Community' and whether Article 7 or 8 applies.
The following is applicable both for orphan-designated and non-orphan medicinal products:
For example, if company A holds a marketing authorisation in indication A for a product containing substance x (still patented), and company B (a subsidiary of company A) intends to apply for a new stand-alone marketing authorisation for substance x in a new indication B, the product will be considered as 'already authorised' based on the GMA concept, and company B will be required to cover also indication A in its PIP (i.e. Article 8 applies).
The GMA approach will apply to variations, extensions and new marketing authorisation applications falling under the requirements of Article 7 and 8. Where relevant, you should also consider whether a modification to an agreed or ongoing PIP or waiver decision is required in case the GMA concept had not been applied, in order to avoid difficulties at validation of your subsequent regulatory submission.
When an active substance from the 'same marketing authorisation holder' is or will be the subject of two marketing authorisations, one covering orphan indications and another covering non-orphan indications, those marketing authorisations would not be considered as part of the same GMA in light of Articles 7 and 8 of the Paediatric Regulation. In such situation, it is recommended to liaise with the EMA for further clarification of the regulatory implications.
Both the guideline on the elements required to support the significant clinical benefit in comparison to existing therapies of a new therapeutic indication in order to benefit from an extended (11-year) marketing protection and the guideline on a new therapeutic indication for a well established substance provide a definition of what is considered a new indication, i.e.:
For the purpose of the application of Article 8, the same guideline should be followed.
However, case-by-case assessment may be needed for particular situations to define whether a criterion of the 'extended target population' is fulfilled. For example, a modification of the product information may not be considered as a new indication in the following cases:
The Agency encourages applicants to make contact in advance of a planned submission in order to clarify paediatric requirements and to anticipate any regulatory issues that could prevent the validation of the application.
A 'combined term' is used in some cases to further characterise a pharmaceutical form. It may be a combination of dosage forms, a combination of dosage forms and routes or methods of administration, container or administration device.
Where a combined term is constructed by a combination of a dosage form and a container or administration device, it may not in certain cases be considered as a new pharmaceutical form in the light of Article 8 of the Paediatric Regulation.
In addition, a change of standard term for a presentation of a medicinal product resulting from the deletion of a solvent is also not considered to be a new pharmaceutical form.
The Agency encourages applicants to make contact well in advance of a submission in order to clarify paediatric requirements and to anticipate any regulatory issues which could prevent validation of an application.
Applications under Article 10c of Directive 2001/83/EC (informed-consent applications) are not excluded from the scope of the Paediatric Regulation. The applicant will have to declare in the application form whether the conditions as specified in article 7 or 8 apply to their informed consent application. Any subsequent application for a new indication, pharmaceutical form or route of administration would need to comply with the requirements as laid down in article 8, if the medicinal product is covered by a Supplementary Protection Certificate (SPC) or a patent qualifying for an SPC.
Article 7 of the Paediatric Regulation applies to fixed-dose combination medicinal products, which were not authorised in the European Union by 26 July 2008.
The global marketing authorisation (GMA) concept in relation to the fixed-dose combination concerned, together with the notion of 'same marketing authorisation holder' (MAH) are used to determine whether an application for a fixed-dose combination product concerns a medicinal product which is authorised or not as a fixed-dose combination in the European Union, and therefore whether Article 7 or 8 applies (see question 2.1. 'When is my product considered 'not authorised in the Community?').
Example 1: Fixed-combination medicinal product authorised: substance A 5 mg / substance B 10 mg tablets:
The application concerns substance A 5 mg / substance B 10 mg capsules (not tablets) by the same MAH. This will be considered part of the GMA, therefore Article 8 applies, due to the change in the pharmaceutical form.
Example 2: Fixed-combination medicinal product authorised: same as above (substance A 5 mg / substance B 10 mg tablets):
The application however concerns substance A 10 mg / substance B 10 mg tablets by the same MAH. This is not a new medicinal product as the medicinal product is already authorised and this new strength falls within the same GMA. Therefore, Article 7 does not apply and neither does Article 8, as the conditions of this article are not met. A change in strength does not trigger Article 8.
Article 7 of the Paediatric Regulation applies in principle to advanced-therapy medicinal products (ATMPs).
If a medicinal product is authorised for a paediatric indication following completion of an agreed paediatric investigation plan and the product has already been marketed with other indications in a Member State, the marketing-authorisation holder should place the product including the paediatric investigation on the market of the Member State where the medicinal product is authorised for the paediatric indication within two years of the date of the marketing authorisation for the paediatric indication.
This applies to nationally authorised and centrally authorised products.
The date of placing the medicinal product on the market should be understood as the date of first release into the distribution chain.
The Agency makes these deadlines public for all medicinal products that are authorised for a paediatric indication, following completion of an agreed paediatric investigation plan. For the complete list, also known as the Article 33 Register, see Deadlines for placing paediatric medicines on the market.
When a product has been placed on the market of the relevant Member State(s) with a new paediatric indication after completion of an agreed PIP, the marketing-authorisation holder can declare it by informing the EMA Paediatric Medicines Office via the IRIS platform.
EMA will update the Article 33 Register accordingly.
The Agency will make this information public.
The requirements described above apply to nationally and centrally authorised products, when the marketing-authorisation holder has the intention to discontinue placing the product on the market in any country of the European Union.
The date of discontinuation of placing the medicinal product on the market should be understood as the date of the last release into the distribution chain.
Article 28(3) of the Paediatric Regulation states, 'if the application complies with all the measures contained in the agreed completed PIP and if the summary of product characteristics reflects the results of studies conducted in compliance with that agreed PIP, the competent authority shall include within the marketing authorisation a statement indicating compliance of the application with the agreed completed PIP.'
If the application is for a centralised marketing authorisation, the compliance statement is included in the Commission decision. Decisions granting a marketing authorisation are published in the Community register of medicinal products for human use.
Since November 2012, if the application is for varying the terms of an existing centralised marketing authorisation, the compliance statement will be included in the technical dossier of the marketing authorisation. Therefore, when the opinion is adopted by the Committee for Medicinal Products for Human Use (CHMP), the Agency provides the holder with a 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 on the webpage for the medicine, see European public assessment reports (EPARs).
For details on paediatric requirements when submitting an application for a new marketing authorisation, an extension or type-II variation to a marketing authorisation, see Paediatric requirements for marketing authorisation applications.
See Procedural advice on paediatric applications for information on how to apply for a compliance check.
Early involvement of clinical research networks may help to develop a PIP in a number of ways, and should be considered when preparing the application, as recommended in the EU Guideline on the Format and content of PIP and waiver applications.
Enpr-EMA, which is coordinated by the Agency, provides a contact point for a number of specialty and multi-specialty networks. Areas of expertise that can be offered by Enpr-EMA members are reported in the Enpr-EMA database.
Networks may provide assistance in the following areas:
Paediatric research network expertise is available for the entire drug development cycle, from scientific idea to clinical studies of the PIPs and safety follow-up after marketing authorisation. For recommended timing of network consultations please see Enpr-EMA Working group on public-private partnership: Network consultation recommendation
The opinion of and feedback from Enpr-EMA networks is of great value to the PDCO in order to best inform discussions on Paediatric Investigation Plans (PIPs). There are essentially three main routes of ad-hoc communication between individual Enpr-EMA networks and PDCO:
Official representatives of Enpr-EMA networks may at any time contact PDCO via letter or e-mail (enprema@ema.europa.eu) in order to communicate matters of general concern regarding paediatric clinical research.
The PDCO may sometimes seek the opinions of Enpr-EMA networks on matters related to paediatric clinical research. The PDCO's request may concern general paediatric clinical questions or arise from the evaluation of a specific PIP. In the latter case PDCO's requests will not disclose any confidential product-related information.
Sometimes the PDCO may also recommend that a PIP applicant should seek advice from an Enpr-EMA network with regard to their ongoing PIP procedure.
Responses from the networks should be given as consolidated network advice by the official Enpr-EMA representative as opposed to the personal opinion of a key opinion leader.
Enpr-EMA networks may sometimes wish to communicate expected or experienced challenges concerning the conduct of (a) trial(s) included in an initial PIP under PDCO evaluation or in an already agreed PIP. In these cases - in order to comply with confidentiality requirements - communication should be between the PIP applicant and the PDCO, not between a specific network and the PDCO. The network involved should communicate with the PIP applicant and agree with them to contact the PDCO in the framework of a procedure for the agreement of an initial PIP or a procedure for the modification of an agreed PIP, as applicable.
Networks should follow the process below: