Are You Prepared to Address International Pediatric Plan Requirements?

Did you know that pediatric plans are a requirement for virtually all new medicines, and not just those identified as available for children? The only exceptions are those medicines that are on the waiver list or are specifically exempted by the FDA or EMA.

Although some labeling requirements for children existed since 1979, more than 80 percent of listed medication labels didn’t have prescribing information for children and were being used off label, even in hospitals—a potentially hazardous situation that the FDA and EMA sought to rectify. Therefore, more stringent pediatric requirements have been set in place in both the US and EU to make additional medications more safely available to young patients.

Both the EU and US had similar goals: to improve the health of children through high quality, ethical research that would increase the availability of authorized medicines for children and increase information for caregivers, without unnecessary studies being conducted on children and without delaying authorization for adults. Pediatric investigation plans (PIPs) are the EU Pediatric Regulation’s main tool to ensure that previously unmet therapeutic needs in children are researched and appropriate medicines are developed. Pediatric study plans (PSPs) are required by the FDA in the US to identify needed pediatric studies early in drug development.

Collaboration has become the key to improvement

Since 2007 when the EMA and FDA agreed upon collaboration and common principles of interaction, a great deal of progress has been made. A monthly teleconference to discuss product specific pediatric drug development and general scientific, regulatory and safety issues has been held. Japan PMDA and Health Canada joined, initially as observers in 2009 and 2010, respectively, and both are now active participants. Documents are exchanged through a secure link, Eudralink.

This communication does not mean that pediatric development programs will have exactly the same protocols or ask the same question or even arrive at the same regulatory decisions. However, the objectives of the exchanges are valid – to avoid exposing children and neonates to unnecessary trials and to enhance the science while decreasing the risk.

Where are we today?

Requirements indicate that not filing PSPs and PIPs properly or on time could prevent Marketing Authorization Applications (MAAs) and New Drug Applications (NDAs) from being evaluated.

On 26 October 2017 the European Commission presented its report, “10 Years of the EU Pediatric Regulation,” to the European Parliament and Council. The report reveals that the regulation’s system of obligations, rewards and incentives has had a positive impact on the development of pediatric medicines in the EU. From 2007 through 2016, more than 260 new medicines were authorized for use by children through new marketing authorizations and indications, and, the number of PIPs completed grew considerably, with over 60% finalized in the last three years. In 2017, there were over 1000 agreed PIPs.

According to the report, “One of the Regulation’s undisputed achievements is bringing more attention and financial investment to pediatric development... Pharmaceutical companies now consider pediatric development as an integral part of the overall development of medicinal products...”

More progress to come.

While this impact is encouraging, positive results are not evenly spread among therapeutic areas. The regulation appears to be most effective when adult and pediatric needs overlap. Fewer advances have been made in diseases that are rare or unique to children.

The European Commission does not recommend re-opening the legislation at this stage. It will, however, evaluate both pediatric and orphan regulations to better understand their combined effects and why the orphan reward does not seem to be driving pediatric development for rare diseases. Findings of this combined analysis are expected to be delivered in 2019.

Meanwhile, the European Commission and EMA are expected to begin working on pragmatic measures to streamline application and implementation of the regulation. We also anticipate seeing a revision of the US FDA’s Safety and Innovation Act (FDASIA), which was signed into law in 2012. When available, the report will appear on the FDA site.

Where can you learn more about the evolution of pediatric trials and how pediatric plan requirements could impact your clinical development?

Download the latest white papers from SynteractHCR’s vice president for global medical and regulatory affairs, Dr. Martine Dehlinger-Kremer. Dr. Dehlinger-Kremer is the chair of the European Forum for Good Clinical Practice (EFGCP) Children’s Medicines Working Group, chair of the European CRO Federation (EUCROF) Pediatric Working Group and member of Working Parties of Enpr-EMA, the European Network of Pediatric Research at the European Medicines Agency. Or contact SynteractHCR at +1 760 268 8200.


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