Euro Convergence: EU pediatric medicines regulatory framework needs simplification, optimization

Regulatory NewsRegulatory News | 12 May 2021 |  By 

Industry would like to see some “pragmatic” changes to the regulatory process for pediatric medicines in the EU, according to a recent presentation at RAPS Euro Convergence 2021.
These changes include incorporating scientific discussion throughout a product’s life cycle, comparable reporting requirements for pediatric trials to those for adult trials, and optimization and simplification of pediatric investigation plan (PIP) procedures and compliance checks, said Thomas Kühler, head of global regulatory science and policy for Sanofi’s EU, Africa, Middle East and Eastern Europe efforts.
When the Pediatric Regulation (EC No. 1901/2006) came into effect in 2007, the goal was to create an environment where pediatric medicines could be researched and made available without “studies on children or delaying authorization for adults.” The regulation created the concept of pediatric investigation plans (PIPs) and the Pediatric Committee (PDCO).
In a report from the European Commission (EC) analyzing 10 years with the EU Pediatric Regulation, the EC said 260 new medicines had been authorized and over 1,000 PIPs agreed on. However, Kühler argued in his presentation that this report showed the EU Pediatric Regulation was only partly successful.
“What was not in the report—but this was my conclusion—is that if it takes 1,000 PIPs to create 260 new medicines, the efficiency or the yield is not very high,” he said. “You only have a 25% yield or something in that neighborhood. So, I would argue, then, that most pediatric investigations indeed did not deliver on expectations.”

Scientific advice tool
Kühler then outlined a series of issues in pediatric medicine regulation in the EU, beginning with scientific advice that takes places in the non-clinical and early-stage clinical trial setting. Here, “the submission of PIPs is a binary item,” he said. “It’s all or nothing. You have to do it at the very beginning. There is really no flexibility.” Problems can arise, however, when a PIP is required to be submitted but there is limited data available on new medicines, endpoints for clinical trials haven’t been determined, and the mechanism of action for the medicine isn’t known.
“I think the solution to this from the industry point of view is really quite simple,” he said. Kühler proposed an iterative, dynamic process involving representatives from the European Medicines Agency’s human safety committee (EMA’s CHMP), PDCO and other stakeholders. The goal would be to build a pediatric development strategy that allows PIPs to be submitted with the best-known science and adequate knowledge around a new pediatric medicine. This system could reduce follow-up modifications to PIP and ensure a PIP is more likely to be completed, Kühler said.
Optimizing PIPs, simplifying compliance checks
Kühler also suggested changes to the PIPs themselves: namely, that PIPs should be “developed on robust evidence instead of assumptions” which would allow PDCO to more quickly review the PIP and “a decision on the key binding elements could be promptly delivered.” The most common PIP modifications occur when there is a change in the timeline, such as a delay in when a study is completed, he noted.
“The scientific advice, and the discussion and the science that goes into PIP has to be a little bit more mature than it is today,” he said.
Another consideration for PIPs is simplifying the compliance checks that occur to ensure the key binding elements in a PIP are being followed. In particular, partial compliance checks mandated by EMA are not part of the pediatric regulation but are a “significant regulatory burden” that potentially delay approval of pediatric medicines, Kühler said. EMA also requires a full compliance check before a sponsor can begin the assessment process. Kühler argued that these compliance checks can happen in parallel with assessment of the pediatric data.
Further, Kühler said that rather than having compliance checks occur once a month, they should be happening on a continuous basis as data are submitted.
“If you take all of these things together and just think about it, who is losing out? To some extent, I think industry and EMA or the regulators are losing out, because we spend a lot of time on extra bureaucracy which is not mandated, and actually hasn’t shown that there is any value to it,” he said.
“The stakeholder who is losing out is society and its patients, because it just takes a longer time for new drugs to reach the marketplace,” he added.
Aligning clinical study reporting requirements
Currently, clinical study reporting requirements for pediatric studies call for a report to be submitted within 6 months of completion, which is “substantially shorter” than the 12-month window for non-pediatric studies. Kühler said that there is evidence that this shorter turnaround time for pediatric clinical study reports has not made a difference in public health.
“Why are the timelines not aligned?” he asked. “And why do we not just do one reporting? Why do we do two? Here, we ask for the reporting to be streamlined and aligned.”
Euro Convergence 2021


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