Posted May 12, 2021 | By Jeff Craven
According to a recent presentation at RAPS Euro Convergence 2021, the industry would like to see some “pragmatic” changes in the regulatory process for pediatric medicines in the EU.
These changes include the inclusion of scientific discussion throughout the life cycle of a product, similar reporting requirements for pediatric studies to those for adult studies, and optimization and simplification of pediatric investigation plan (PIP) procedures and compliance controls, said Thomas Kühler, head of the global regulatory science and policy for Sanofi’s efforts in the EU, Africa, the Middle East and Eastern Europe.
When the Pediatric Regulation (EC No 1901/2006) entered into force in 2007, the aim was to create an environment in which pediatric medicines could be researched and made available without “researching children or delaying the authorization of adults “. The regulation created the concept of Pediatric Investigation Plans (PIPs) and the Pediatric Committee (PDCO).
In a report by the European Commission (EC) analyzing 10 years of the EU pediatric regulation, the EC said that 260 new drugs had been approved and more than 1,000 PIPs had been agreed. However, Kühler argued in his presentation that this report showed that the EU pediatric regulation was only partially successful.
“What was not in the report – but this was my conclusion – is that if it takes 1,000 PIPs to make 260 new drugs, the efficiency or yield is not very high,” he said. “You only have 25% yield or so in that neighborhood. So I would say that most pediatric studies have indeed failed to meet expectations. “
Scientific advice tool
Kühler then outlined a range of issues in pediatric medicine regulations in the EU, starting with scientific advice taking place in the non-clinical and early phase of clinical trials. 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 really is no flexibility.” However, problems can arise when a PIP has to be submitted, but limited data is available on new drugs, the clinical endpoints studies have not been established and the mechanism of action of the drug is unknown.
“I think the solution to this is really quite simple from an industry point of view,” he said. Kühler proposed an iterative, dynamic process involving representatives from the European Medicines Agency’s Human Safety Committee (EMA CHMP), PDCO and other stakeholders. The goal would be to develop a pediatric development strategy that would allow submitting PIPs with best known science and sufficient knowledge about a new pediatric drug. This system could reduce subsequent changes to PIP and ensure that a PIP is likely to be completed, Kühler said.
Optimize PIPs, simplify compliance checks
Kühler also suggested changes to the PIPs themselves: namely that PIPs “should be developed on the basis of robust evidence rather than assumptions”, which would allow PDCO to assess the PIP more quickly and “make a decision on key binding elements immediately. taken. ” The most common PIP changes occur when there is a change in the timeline, such as a delay in completing a survey, he noted.
“The scientific advice, and the discussion and science that goes into PIP, should be a little bit more mature than it is today,” he said.
Another consideration for PIPs is to simplify the compliance checks that take place to ensure that the main binding elements in a PIP are followed. Particularly, partial compliance checks imposed by the EMA are not part of the pediatric regulation, but represent a “significant regulatory burden” that may delay the approval of pediatric medicines, Kühler said. EMA also requires a full compliance check before a sponsor can begin the review process. Kühler argued that these compliance checks could take place simultaneously with the review of the pediatric data.
Furthermore, Kühler said that instead of having compliance checks done once a month, they should be done continuously while the data is submitted.
“If you put all these things together and just think about it, who will lose out? To some extent, I think the industry and the EMA or the regulators are losing it because we spend a lot of time on extra bureaucracy that is not mandatory, and has actually not shown any value to it, ”he said.
“The stakeholder that is losing is society and its patients because it just takes longer for new drugs to hit the market,” he added.
Alignment of reporting requirements for clinical studies
Currently, the reporting requirements for clinical studies for pediatric studies require a report to be submitted within six months of completion, which is “significantly shorter” than the 12-month window for non-pediatric studies. Kühler said there is some evidence that this shorter turnaround time for pediatric clinical trial reports has made no difference to public health.
“Why aren’t the timelines aligned?” he asked. “And why don’t we do one report? Why are we doing two? Here we ask for the reporting to be streamlined and coordinated. “
Euro convergence 2021
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