What is a Paediatric Investigation Plan (PIP)?
The European Medicines Agency (EMA) requires sponsors to follow Paediatric Investigation Plan (PIP) guidelines as part of the regulatory process for developing medicines intended for children. While other regulatory bodies like the FDA and MHRA have similar requirements, the EMA’s PIP guidelines are unique in their templates, submission platforms, and timelines. This article focuses on the essential guidelines for drug development in EU countries.
The PIP ensures companies obtain necessary data through studies in children. This supports medicine authorization for paediatric patients.The PIP outlines the timing, design, and objectives of paediatric studies. It includes details on age groups, endpoints, and formulation considerations. Sponsors must agree on this legally binding plan with the EMA’s Paediatric Committee (PDCO). They need this agreement before receiving marketing authorization for new medicines, indications, formulations, or administration routes.
A well-prepared Paediatric Investigation Plan is not just a regulatory hurdle. It is a strategic tool that guides medicine development for children. It ensures clinical research is scientifically robust, ethically sound, and directly relevant to paediatric patients.
Related Insight:
Designing clinical trials for children presents unique ethical, regulatory, and practical challenges. For a deeper dive into these complexities and best practices, read our related article: Things to consider when designing a clinical trial involving children
Why is a Paediatric Investigation Plan Required?
Historically, many medicines used in children were not specifically tested for efficacy, safety, or dosage in this population. This led to fewer treatment options for children, or to off-label use with associated risks. The introduction of the Paediatric Regulation No 1901/2006 in the European Union aimed to improve children’s access to appropriately researched and authorized medicines.
The PIP requirement serves several critical purposes:
- Promotes safe and effective use of medicines in children: By mandating research in paediatric populations, it reduces the risks of adverse effects and suboptimal dosing and avoids redundant or ethically questionable studies.
- Encourages innovation: PIP guidelines incentivize pharmaceutical companies to develop paediatric formulations and indications, which may not otherwise be commercially attractive.
- Supports regulatory harmonization: Establishes a standardized approach to paediatric medicine development across the EU, facilitating faster access to new treatments for children.
Cases in Which a PIP Is Not Required
- If studies in children are not feasible or appropriate (e.g., if the disease only affects adults), investigators should request a waiver explaining why they won’t submit a PIP.
- If investigators need to delay paediatric studies until they gather more data (from adult or healthy volunteer studies), they can seek a deferral and explain their reasoning.
- If a sponsor plans to request marketing authorization through the hybrid route, they don’t need to submit a PIP.
When Must a Paediatric Investigation Plan Be Written and Submitted?
Sponsors should consider the paediatric population and the PIP early in the development phase. Writing a PIP is a time-consuming process, and review by the EMA can also take up to a year, including negotiations. Usually, sponsors write the PIP at the end of Phase I studies, and they should secure agreement on the plan before starting Phase III (pivotal) trials. This ensures that developers can integrate paediatric considerations into the overall development strategy, and that they can plan and conduct studies in children in parallel with or following adult trials.
Even if applicants develop a drug for a disease that only affects children, they must still submit a PIP and obtain EMA approval. Writing the PIP forces the applicant to consider all aspects of this special population early in the development and initiates dialogue with the EMA.
Regulatory requirement:
- For new medicines: sponsors must submit a PIP before they file the marketing authorization application (MAA).
- For new indications, formulations, or routes of administration: sponsors need a PIP if the change could be relevant for paediatric use.
Who Writes and Submits the PIP?
The responsibility for writing and submitting a Paediatric Investigation Plan lies with the marketing authorization applicant. Collaboration among several stakeholders is essential:
- Regulatory Affairs Professionals: Lead the drafting, submission, and management of the PIP, ensuring compliance with EMA guidelines.
- Clinical Development Teams: Design paediatric studies, select endpoints, and define age groups and formulations.
- Pharmacologists and Formulation Scientists: Address specific challenges in paediatric dosing and drug delivery.
- Medical Experts: Provide input on disease epidemiology, ethical considerations, and paediatric patient needs.
After drafting the PIP, investigators submit it to the EMA’s Paediatric Committee (PDCO), which reviews the plan, requests modifications if necessary, and ultimately approves or rejects the proposal. The process may involve several rounds of negotiation and revision. At the time of MAA, the applicant should indicate if they have followed the plan or justify any deviations with a proper rationale.
Conclusion: The Value of Thoughtful Paediatric Investigation Plan (PIP) Guidelines
By understanding what a Paediatric Investigation Plan is, why it is required, when it must be submitted, and who is responsible, sponsors can navigate the complexities of paediatric drug development and contribute to closing the gap in child health therapeutics.
