Regulatory News: How are FDA and EMA expectations for Pediatric Investigation Plans (PIPs) in oncology evolving?

Regulatory expectations for pediatric oncology development are shifting, with greater scrutiny placed on how sponsors justify moving into pediatric studies—not only whether a mechanism of action could be relevant. Recent reflections from the European Medicines Agency (EMA) alongside ongoing alignment with the U.S. Food and Drug Administration (FDA), signal a more structured approach to assessing proof of concept and overall weight of evidence earlier in development.^1,2

For regulatory teams, these signals raise an important question: does your current pediatric strategy stand up to the level of challenge regulators are now applying?

What is driving this change in Pediatric Investigation Plans (PIPs)?

In a draft concept paper published in March 2026, the EMA outlined plans to develop guidance for evaluating nonclinical proof of concept supporting pediatric oncology trials.¹ The focus moves beyond a mechanism of action justification alone and toward a totality of evidence view that considers disease biology, data relevance and translatability.

This reflection responds to several challenges regarding  oncology PIPs:

• Pediatric cancers are biologically distinct from adult cancers, limiting simple extrapolation
• Clinical trial feasibility is constrained by small patient populations
• Regulatory decisions increasingly rely on the quality and relevance of nonclinical data

Together, these factors are leading regulators to question whether existing evidence truly supports the initiation of pediatric trials.

“Scientific and technological advances in the available in vitro and in silico tools are fuelling regulatory momentum towards acceptance, and subsequent requirement, of big data weight of evidence approaches across all aspects of drug development”

-Lesley Reeve, Senior Director, Global Regulatory Strategy, Fortrea

How pediatric oncology expectations are changing in practice?

For many oncology programs, pediatric strategy decisions are required early—often by the end of Phase I or early Phase II in the EU, with closely related expectations for FDA Pediatric Study Plans later in development under the Pediatric Research Equity Act (PREA).³

Under the EMA’s proposed thinking, sponsors should be prepared to justify pediatric development using a structured weight of evidence approach that may include:

• Relevance of the mechanism of action to pediatric tumour biology
• Understanding of disease pathways and biomarkers
• Data from same in class or related assets
• Rationale for how nonclinical findings translate to pediatric settings

Programs built primarily around precedent or high level assumptions may face increasing challenge under this lens.

Why early regulatory strategy matters more now

Regulatory expectations rarely shift overnight. They evolve through concept papers, scientific advice discussions and changes in review behavior—well before formal guidance is issued.

This creates both risk and opportunity. Teams that wait to address pediatric strategy late in development may encounter unexpected data requests or misalignment between regions. Those that plan early can shape development plans while flexibility still exists.

Fortrea integrates regulatory strategy, intelligence and execution across the full asset lifecycle—helping sponsors make confident decisions earlier and design development programs that stand up to regulatory and commercial scrutiny. Through continuous regulatory intelligence, regional fluency and thoughtful use of advanced technology, we can reduce risk, prevent re-work and help keep development on track from early planning through post approval commitments.

Taking proactive steps toward pediatric oncology regulatory readiness

If you are developing an oncology asset with potential paediatric relevance—or preparing for upcoming FDA or EMA interactions—now is the right time to reflect on whether your regulatory strategy is fully aligned with current regulatory thinking:

• Review project objectives in light of evolving FDA and EMA expectations
• Assess whether available data adequately support paediatric development plans
• Identify gaps while there is still time to generate or reposition evidence
• Prepare for more meaningful regulatory engagement across regions

Fortrea’s Regulatory Strategy group works with Sponsors to review objectives, assess available data and provide practical recommendations on how best to proceed across regions and milestones.

Start the conversation early with our team to test your objectives, data and assumptions against evolving FDA and EMA expectations. Set up a meeting with us today

References

1. European Medicines Agency. Concept paper on the development of a reflection paper on proof-of-concept data to support the development of anti-cancer medicinal products for paediatric patients. https://www.ema.europa.eu/en/documents/scientific-guideline/concept-paper-development-reflection-paper-proof-concept-data-support-development-anti-cancer-medicinal-products-paediatric-patients_en.pdf . Published 13 March 2026. Last accessed May 2026.
2. Common Commentary - EMA/FDA Common issues requested for discussion by the respective agency (EMA/PDCO and FDA) concerning paediatric oncology development plans (Paediatric Investigation Plans [PIPs] and initial Pediatric Study Plans [iPSPs]). https://www.ema.europa.eu/en/documents/other/common-commentary-emafda-common-issues-requested-discussion-respective-agency-emapdco-and-fda-concerning-paediatric-oncology-development-plans-paediatric-investigation-plans-pips-and-initial-pediatric_en.pdf . Published 26 March 2026. Last Accessed May 2026.
3. U.S. Food and Drug Administration. Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Pediatric Study Plans. Guidance for Industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pediatric-study-plans-content-and-process-submitting-initial-pediatric-study-plans-and-amended . Published July 2020. Last Accessed May 2026.
4. European Parliament and Council. Regulation (EC) No 1901/2006 on medicinal products for paediatric use. https://www.legislation.gov.uk/eur/2006/1901/body/adopted . Last updated December 2020. Last accessed May 2026.
5. European Medicines Agency. Paediatric Investigation Plans (PIPs). https://www.eudrac.com/services/medicinal-products/research-development/paediatric-investigation-plan-pip . Last accessed May 2026.

FAQs

What is a Paediatric Investigation Plan (PIP) or Pediatric Study Plan (PSP)?

As defined in Regulation (EC) No 1901/2006 and the Pediatric Research Equity Act (PREA), a Paediatric Investigation Plan (PIP) or Pediatric Study Plan (PSP) is required in the EU and U.S., respectively, to support the authorisation of a medicine for children. ^3,4,5

In EU, the regulation obliges sponsors of all new medicines to conduct studies in children, unless specifically exempted.  A PIP is expected if the target or pathway is relevant to paediatric malignancies, even if the adult tumour type does not occur in children. ^4,5

In EU, a PIP should be submitted no later than completion of adult human pharmacokinetic (PK) studies (typically end of Phase 1/early Phase II). For oncology drugs, there has been an increasing trend in companies submitting PIPs based on the molecule's mechanism of action rather than on its targeted adult indication. ^4,5