Efficiently adapting regulatory compliance requirements from the Food and Drug Administration (FDA) to the European Medicines Agency (EMA) across nonclinical, clinical, and quality sections of the Paediatric Investigation Plan (PIP) is essential.
While the FDA has strict requirements around studies in children – through the initial Paediatric Study Plan (iPSP) and, more recently, the Paediatric Research Equity Act (PREA), which allows the FDA to require paediatric studies – the EMA’s PIP follows a different, rigorous regulatory framework.
Get your data lined up
Specifically, sponsors must ensure that all data the EMA deems to be necessary is obtained through studies in children. As noted on the EMA website, “all applications for marketing authorisation for new medicines have to include the results of studies as described in an agreed PIP, unless the medicine is exempt because of a deferral or waiver.”
Once the PIP is “fully completed”, sponsors can request the Paediatric Committee (PDCO) to carry out a compliance check before submitting a marketing authorisation application. A compliance check is verification that the studies and measures agreed to in the PIP have been carried out.
Getting the PDCO opinion
The PDCO’s opinion is considered to be final, allowing the sponsor to begin the MAA process, either:
- To use the product in adults and develop a paediatric plan later, drawing on existing data with a plan to gather more data from trials in children.
- To pursue MAA for a children-specific product, with agreement to carry out clinical trials in children in line with the PIP as agreed in the PIP compliance check.
- To add new paediatric indications, new paediatric routes of administration, or new paediatric formulations (excluding new strengths) to an already authorised medicine.
Those companies that gain a positive PDCO opinion are likely to be successful in their MAA since they have already provided adequate safety, efficacy and quality data.
Paediatric patients are the priority
The PIP is a rigorous path, which is understandable, since the EU is a risk-averse market. The protection of paediatric patients is the priority, but there is also a need to ensure publicly funded treatments do exceed the standard of care.
The rewards for sponsors willing to take the necessary steps and follow the PIP requirements are notable. Unlike the US, companies with paediatric products enjoy continued product tenders in the EU without the stress of competition. As noted in the EMA’s Q&A on PIP compliance verification, PIP products benefit from:
- a six-month extension of the supplementary protection certificate (SPC), for the medicinal products that are covered by a SPC or a patent qualifying for a SPC
- a two-year extension of the market exclusivity, for the medicinal products that are orphan designated
- a 10-year period of market protection, including an 8-year period of data exclusivity, in the framework of a paediatric-use marketing authorisation (PUMA), preventing generic applications to rely on the dossier of the reference product or placing the product on the market.
The right advice
To get there, though, you need to follow the scientific advice, speak with the right people – the rapporteur, coordinator, Small and Medium Enterprise office and PIP office – get agreement, speak the language of the EU from a cultural perspective, and follow the defined steps.
Our objective with our synchronisation approach is to mitigate missteps that we see non-EU companies taking when they don’t understand the deeper regulatory requirements and cultural nuances involved in bringing products to the EU market.
Those companies that gain a positive PDCO opinion are likely to be successful in their MAA.