Paediatric Medicines Under the EU Legislative Reform

The EU pharmaceutical legislation reform represents a major update to the regulatory framework for human medicines. Expected to enter into force in 2026, with a transition period running to 2028, the reform aims to modernise and simplify the current system so that it remains effective, proportionate and responsive to evolving scientific and healthcare developments.

As part of the reform, several long-standing regulations, including the Paediatric Regulation (EC) No 1901/2006, will be repealed and their provisions incorporated into a consolidated legislative framework. For paediatric medicines, many of the fundamental principles of the current legislation are retained, including the use of Paediatric Investigation Plans (PIPs), waivers, deferrals and the Paediatric Use Marketing Authorisation (PUMA) pathway. However, the reform also introduces important structural and procedural changes, including the abolishment of the Paediatric Committee (PDCO), potential earlier integration of paediatric planning into development programmes, revised approaches to waivers and incentives, and strengthened transparency and post-authorisation obligations.

Collectively, these changes seek to create a more flexible and efficient framework for paediatric medicine development, while continuing to ensure that the therapeutic needs of children are considered throughout the development, authorisation and lifecycle management of medicinal products.

EMA Organisation Changes: Integrating Paediatric Expertise into a New Framework

Part of the proposed EU pharmaceutical reform aims to improve the functioning and efficiency of the EU regulatory system by simplifying the governance structure of the EMA. Under the proposal, the number of scientific committees for human medicines will be reduced from six to two; the Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance Risk Assessment Committee (PRAC) (Figure 1).

Figure 1: Changes to the structure of EMA committees

Under this model, committees such as the PDCO will no longer operate as standalone decision-making bodies. Instead, their responsibilities will be integrated into a more flexible scientific support framework. Specialist expertise to support the CHMP and PRAC will be maintained through working parties, expert panels, patient advisory groups, and pools of scientific experts, such as the European Network of Paediatric Research (Enpr-EMA), which is retained within the proposed legislation.

Enpr-EMA brings together patient representatives, academics, medicines developers, investigators, and research centres with expertise in paediatric research. Its role includes identifying priorities for the development of medicines for children, particularly in areas of unmet medical need, coordinating paediatric research activities, strengthening scientific and administrative expertise across Europe, and avoiding unnecessary duplication of studies involving children. Therefore, although the PDCO would cease to exist as a standalone committee, the specialist paediatric expertise would remain embedded within the EU regulatory framework through these scientific support structures.

Obligations, Incentives and Rewards for Paediatric Medicines

According to the proposed EU pharmaceutical reform “…market forces alone have proven insufficient to stimulate adequate research into, and the development and authorisation of, medicinal products for the paediatric population”. While this challenge has long been recognised and is already addressed under the current EU paediatric framework through a system of obligations, incentives and rewards, the proposed legislation seeks to retain and further refine these mechanisms to continue encouraging the development of medicines for children.

Submission Timing of PIPs

Under the reformed regulation, PIPs and waiver requests should be submitted to the Agency before the initiation of clinical safety and efficacy studies (except for in duly justified cases). This represents a change from the current Paediatric Regulation (EC) No 1901/2006, under which PIP applications are generally required following completion of adult pharmacokinetic studies. It remains unclear how this new requirement will be interpreted in practice and applied within the drug development timeline.

However, the revised wording may necessitate consideration of paediatric development strategies at an early stage of product development and in time for studies to be conducted in the paediatric population. The existing Paediatric Regulation already requires a PIP when seeking a new indication, new pharmaceutical form or route of administration for an already-authorised product, which is covered by an SPC or patent. The PIP obligation is extended to also cover applications for a new strength of a product.

Initial Paediatric Investigation Plans (PIPs)

The proposed regulation formalises the concept of stepwise Paediatric Investigation Plans (sPIPs), which has been in pilot by the EMA/PDCO in recent years. This is in recognition that, in some cases, the paediatric development programme needs to be progressively developed and refined as scientific knowledge increases. The regulation states that an initial PIP may be used where the active substance has not yet been authorised in any medicinal product in the EU and is intended to diagnose, prevent or treat a novel or existing paediatric condition through a new mechanism of action, or where the EMA accepts a duly justified request from the applicant.

Current EMA guidance on stepwise PIPs (which may be subject to change as we transition to the new EU regulations) describes several circumstances in which a stepwise PIP may be appropriate, such as; first-in-disease medicines (including rare diseases only recently identified in children), products with mechanisms of action that are not yet fully characterised and may be affected by age-related developmental changes, and medicines with multiple potential development pathways intended to address significant unmet paediatric needs where supporting adult data are limited. Although the specific provisions may be adapted as the new legislation is implemented, the current guidance remains informative as it reflects the underlying regulatory rationale and offers an indication of how regulators may approach the assessment and implementation of initial PIPs in the future.

Waivers and the Introduction of MoA-based PIP Requirements

As with current legislation, a waiver may be granted where a medicinal product offers no significant therapeutic benefit over existing methods of diagnosis, prevention, or treatment, where a medicinal product is likely to be ineffective or unsafe in the paediatric population, or where the relevant disease or condition occurs exclusively in adults. However, a key change in the new legislation is that sponsors seeking a waiver on the grounds that the adult disease or condition does not occur in children may be required to consider whether the medicine’s mechanism of action (MoA) could be relevant to a paediatric disease within the same therapeutic area. Where existing scientific evidence supports such potential relevance, the EMA may require the sponsor to implement a MoA-based PIP, even if the proposed adult indication itself is not relevant to the paediatric population. However, it remains unclear how the criteria for a MoA-based PIP will be translated into guidance for sponsors and implemented in practice. Further clarification is needed on how sponsors can ensure that sufficient scientific evidence is available at the time a MoA-based PIP is discussed with regulators.

EMA-Triggered Modifications to PIPs

As already provisioned in the regulation, a Sponsor can request a modification of an agreed PIP if there are difficulties encountered in its implementation. What is new however, is that now the EMA may also trigger request for modifications where new scientific information indicates that the agreed plan, or specific elements of the plan, are no longer appropriate. The sponsor must submit the proposed changes within 60 days, with the EMA responding with a decision on acceptance or refusal within 30 days of the submission.

PIP Deferrals

The EMA may defer initiation or completion of paediatric studies when:

• Adult studies should be completed first.
• Scientific or technical reasons justify postponement.
• Public health considerations support delay.

A distinction in the new regulation is that deferrals will generally be limited to five years but may be extended in justified cases.

Post-Authorisation Requirements

Launch Obligations in all Member States:

Following authorisation of a new paediatric indication, the Marketing Authorisation Holder (MAH) must launch the indication in all Member States where the product is marketed within two years.

Furthermore, to support the continued availability of authorised paediatric indications, MAHs intending to withdraw such a product from the EU market must ensure that appropriate arrangements are in place to maintain patient access to the medicine. Competent authorities must also be notified of the intended withdrawal in sufficient time to allow appropriate measures to be taken.

Incentives and Rewards for Paediatrics Medicines

Paediatric Use Marketing Authorisation Purpose

A dedicated Paediatric Use Marketing Authorisation (PUMA) remains available to encourage the development of off-patent medicines specifically for use in children. PUMA applies exclusively to medicines intended for paediatric indications and requires the generation of data in accordance with an agreed PIP. The authorisation may be supported by published scientific literature and can reference existing authorised medicinal products. In addition, the established brand name of an adult product may be retained where appropriate.

PUMA is not a new concept introduced by the legislative reform; rather, it is an existing mechanism that has been retained to continue incentivising the development of paediatric medicines, particularly by small and medium-sized enterprises (SMEs) and generic medicine developers. Through the PUMA pathway, developers may benefit from dedicated regulatory incentives, including independent regulatory data protection and independent market protection for the authorised paediatric product. These incentives are intended to promote investment in paediatric research and increase the availability of appropriately authorised medicines for children.

Fee Reductions and Funding

The paediatric regulatory framework allows for a range of fee reductions, waivers, and funding incentives for paediatric medicines, as illustrated in Figure 2. These measures have been retained under the proposed EU pharmaceutical reform and continue to support the development of paediatric medicines within the EU.

Figure 2: Scientific support and incentives for paediatric medicines

Orphan Designation and Data Exclusivity

The reform removes the current orphan-specific two-year market exclusivity extension linked to completion of an agreed Paediatric Investigation Plan (PIP). Instead, orphan medicines would become eligible for the same six-month Supplementary Protection Certificate (SPC) extension available under the general paediatric incentive framework, aligning the reward structure for orphan and non-orphan medicines. The reform retains an additional one year of regulatory protection for the approval of a new therapeutic indication that demonstrates a significant clinical benefit over existing therapies. However, it appears that this additional protection is not granted automatically for paediatric indications and depends on the indication meeting the significant clinical benefit criterion.

Transparency and Information

The legislation also introduces enhanced transparency requirements for paediatric clinical trials. Information on clinical trials conducted outside the EU that are included in a PIP or submitted in fulfilment of paediatric obligations must be made available through the European clinical trials database. In addition, a summary of the results of all clinical trials recorded in the database should be published within six months of trial completion, unless this is not possible for justified scientific reasons.

Further transparency obligations continue to apply when a PIP is discontinued. Sponsors will be required to notify the Agency of their intention to discontinue the PIP and provide a justification for doing so at least six months before the planned discontinuation. This requirement is intended to improve regulatory oversight and ensure greater visibility of changes to paediatric development programmes.

Conclusion

The proposed EU pharmaceutical reform represents an important shift in how paediatric medicines will be planned, assessed, and communicated within the EU regulatory framework. While the core objective of ensuring that medicines for children are appropriately studied and authorised remains unchanged, the reform introduces a more integrated approach to paediatric development, with greater emphasis on early planning, lifecycle management, and alignment with broader medicinal product development programmes.

Key changes include the integration of paediatric expertise into new EMA scientific structures, the introduction of mechanism of action-based paediatric considerations, the introduction of initial Paediatric Investigational Plans and strengthened post-authorisation obligations to support the availability of authorised paediatric indications across the EU.

For sponsors, these changes reinforce the importance of considering paediatric requirements from the earliest stages of development and maintaining a proactive regulatory strategy throughout the product lifecycle. Early engagement with paediatric obligations, careful planning of PIPs, and a clear understanding of waiver, deferral and incentive provisions will be essential to support efficient development and avoid delays at the marketing authorisation stage. As implementation guidance continues to emerge, sponsors will need to remain alert to evolving expectations and how these changes may be applied in practice. DLRC can support companies in navigating the new framework, developing practical paediatric regulatory strategies and preparing submissions that align with both scientific and regulatory requirements.

Key Takeaways

• Paediatric requirements remain a major component of EU medicines regulation.
• PDCO as a committee disappears, but paediatric expertise is retained within new EMA working structures.
• Formalisation of stepwise Paediatric Investigation Plans (sPIPs), referred to as initial PIPs in the regulation, to be used in specific situations, recognising that paediatric development may need to evolve as scientific knowledge matures.
• The new regulation removes the current reference to completion of adult pharmacokinetic studies as the trigger for PIP submission, replacing it with broader wording that will require further regulatory interpretation.
• The orphan-specific +2 year orphan market exclusivity reward is removed and replaced by the general paediatric reward of a 6-month SPC extension, which becomes available to both orphan and non-orphan medicines. Waiver requirements may increasingly consider the relevance of a medicine’s mechanism of action to paediatric diseases.
• PUMA incentives are maintained for off-patent medicines.
• Fee reductions, waivers and scientific support for paediatric development are retained.
• New post-authorisation obligations aim to improve the availability and continuity of authorised paediatric medicines across the EU.
• Transparency requirements are strengthened through increased publication of paediatric clinical trial and development information.