Examples
Worked examples
- Is an instance
A company developing a new oncology medicine for adults submits its PIP application to the PDCO by the time its adult pharmacokinetic studies are complete. The agreed PIP requires an age-appropriate oral suspension formulation, paediatric pharmacokinetic and safety studies in adolescents and younger children, and defers the youngest age subsets until adult efficacy data are available. Once the marketing authorisation application includes the results of the studies run under that agreed PIP, the holder becomes eligible for the six-month SPC extension under Article 36 of Regulation (EC) No 1901/2006.
- Is an instance
A sponsor with an orphan-designated medicine for a rare paediatric-onset metabolic disease agrees a PIP covering all relevant age subsets. Because the product holds orphan designation, it is excluded from the SPC-extension route (Article 36(4)) and instead receives the two-year extension of orphan market exclusivity under Article 37 once PIP compliance is confirmed at authorisation.
Counter-examples
Looks similar, but isn't
- Not an instance
A generic manufacturer filing an abridged marketing authorisation application under Article 10 of Directive 2001/83/EC, referencing an already-authorised reference product, is not required to submit a PIP — the Article 7/8 PIP obligation attaches to new active substances and to new indications/forms/routes of patent- or SPC-protected products, not to generic, well-established-use, or traditional-herbal applications.
Editorial commentary
A Paediatric Investigation Plan (PIP) is the development plan a sponsor agrees with the European Medicines Agency’s Paediatric Committee (PDCO) to generate the data needed to support authorisation of a medicine for use in children. It is the central mechanism of the EU’s paediatric medicines framework, Regulation (EC) No 1901/2006, and it functions as a gate: with limited exceptions, an EU marketing authorisation application (MAA) cannot be validated unless it either includes the results of studies conducted in line with an agreed PIP, or the product holds a PDCO waiver.
Legal Basis and Scope
The PIP requirement sits in Article 7 of Regulation (EC) No 1901/2006 for new medicinal products not yet authorised in the EU when the Regulation entered into force, and Article 8 extends the same requirement to new indications, new pharmaceutical forms, or new routes of administration of already-authorised products, where that product is still protected by a patent or a supplementary protection certificate (SPC) eligible for one. Regulation (EC) No 1902/2006 made the accompanying technical and procedural amendments. Products outside patent/SPC protection, and abridged applications relying on well-established use, generic, or traditional-herbal registration routes under Article 10 of Directive 2001/83/EC, fall outside the mandatory PIP requirement.
What a PIP Must Contain
An agreed PIP sets out, for each relevant paediatric age subset (from preterm and term newborns through infants, children, and adolescents), the studies needed to characterise a medicine’s safety, efficacy, and dosing in that population; any age-appropriate formulation development required (for example, an oral liquid or dispersible tablet where the adult product is a large film-coated tablet); and the timelines on which those studies and formulation work will be completed relative to the rest of the product’s development. A PIP is a plan for the whole paediatric development programme, not authorisation for a single trial — individual paediatric clinical trials conducted under an agreed PIP still need their own separate authorisation under the EU Clinical Trials Regulation (EU) No 536/2014 or, for trials outside the EU/EEA, the applicable national framework.
Waivers and Deferrals
Two distinct mechanisms let a sponsor avoid running paediatric studies immediately, or at all, without falling outside the PIP system altogether:
- Waiver — the PDCO agrees that paediatric development is unnecessary or inappropriate for some or all paediatric subsets, most commonly because the condition being treated occurs only in adults (for example, most prostate cancer or age-related macular degeneration indications), or because the medicine is likely to be unsafe or ineffective in children. Waivers can be product-specific or apply across a therapeutic class.
- Deferral — the PDCO agrees that paediatric studies are appropriate but can be completed after the corresponding adult studies, typically so that adult safety and efficacy data exist before children are exposed to the medicine. A deferral does not remove the obligation; the agreed PIP still specifies what will be studied and by when.
A single PIP commonly combines both: a waiver for age subsets where the disease doesn’t occur, and a deferral for the age subsets where it does but adult data should come first.
The PDCO’s Role
The Paediatric Committee (PDCO) is the EMA scientific committee responsible for PIP applications: it assesses each submitted plan, requests modifications where the proposed studies or formulations are insufficient, and issues the final PDCO decision agreeing (or refusing) the plan. It also decides waiver and deferral requests, and its opinions and decisions are published, with confidential commercial information redacted, once adopted.
When a PIP Must Be Submitted
A sponsor must submit a PIP application no later than upon completion of the human pharmacokinetic studies in adults, early enough that PDCO agreement can be reached well before the MAA is filed — a PIP agreed at the last minute leaves no real room to run the paediatric studies it specifies. Because MAA validation checks for either an agreed PIP (with a PDCO compliance statement) or a granted waiver, sponsors that leave PIP submission late risk a validation failure that has nothing to do with the adult clinical package itself.
Rewards and Incentives
Compliance with an agreed PIP is tied to concrete regulatory rewards, not just an obligation:
- Six-month SPC extension (Article 36) — if the MAA includes the results of all studies conducted in line with the agreed PIP, the holder of the corresponding patent or supplementary protection certificate is entitled to a six-month extension of that SPC’s protection period.
- Two-year orphan exclusivity extension (Article 37) — for medicines with orphan designation, the SPC extension route doesn’t apply; instead, PIP compliance extends the ten-year orphan market exclusivity period to twelve years.
- Paediatric-use marketing authorisation (PUMA) — a dedicated authorisation route for developing an already off-patent, off-SPC medicine specifically for paediatric use, carrying its own ten-year data/market protection period for the paediatric-specific data package.
PIP vs. the US Pediatric Study Plan
The EU’s PIP has a US counterpart in the Pediatric Study Plan (PSP) required under the Pediatric Research Equity Act (PREA) and coordinated with the FDA, submitted via FDA’s iPSP portal. The two frameworks pursue the same underlying goal — building a real paediatric evidence base as part of drug development rather than after the fact — but they are separate legal requirements with separate committees, separate content requirements, and separate reward structures; an EU PIP does not substitute for a US PSP or vice versa, though sponsors developing a product globally typically coordinate the two in parallel.
Related CASRAI Content
See CASRAI’s guide on Pharmacovigilance in Clinical Research for how paediatric safety data feeds into ongoing EU/US adverse-event reporting once a product reaches market, and the Clinical Research pillar page for the wider regulatory landscape a PIP sits within.
Also known as
PIP · Paediatric Investigation Plan · Pediatric Investigation Plan
Machine-readable encodings
Use in your systems
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