Tips for avoiding regulatory pitfalls in pediatric drug development

Regulatory NewsRegulatory News | 14 September 2021 |  By 

Developers can improve their chances of success in getting pediatric drugs to market by consulting early with regulators in the US and the EU, understanding regulatory precedence and current context, and having a clearly defined clinical study design, experts advised at RAPS Convergence 2021.
One of the common hurdles in developing a pediatric drug product is navigating the different regulatory requirements in the US and Europe, said Linda McBride, a regulatory consultant who moderated the session.
For instance, EU and US regulations differ on the age range for pediatric patients and on requirements that apply to orphan drugs. They also have different timelines for when sponsors must submit pediatric study plans. 
“Companies often desire to have the same study plan, the same study or studies, to suffice or meet the requirements for both the EU and the US. However, I think the reality is that that cannot always be the case. So, it’s important for us regulatory professionals to make sure our companies know about the differences,” McBride said. “[Regulators] have a desire to collaborate when they can; however, based on the regulations, there may be differences and we as an industry need to support that and understand that, and make sure that we can communicate those internally within our companies.”
Strategy development
One way to help navigate those regulatory differences is to engage both US and European regulators early in the process, said Karl-Heinz Huemer, medical assessor for the Austrian Agency for Health & Food Safety and a member of the Paediatric Committee (PDCO) of the European Medicines Agency (EMA).  
The US FDA and the EMA have regular “cluster calls” to engage in high-level scientific discussions of pediatric drug development plans for new drugs and to keep each other informed about decision making. But those meetings aren’t open to sponsors, since the discussions may include confidential information about other drug applications. However, sponsors can request a parallel scientific advice procedure to meet with both US and European regulators together, Huemer said.
This type of parallel consultation can help everyone to find common ground, Huemer said: “If predefined, a lot of things might be possible.”
Additionally, for sponsors developing pediatric cancer drugs, FDA may invite European regulators to observe “Type F” early advice meetings with sponsors under provisions of the Research to Accelerate Cures and Equity (RACE) for Children Act, which took effect in August 2020.
Huemer also urged sponsors not to delay in beginning their pediatric drug development. “When you start to develop your strategy, my clear recommendation is do it as early as possible because any delay in a discussion and making clear what might be needed, might actually result in problems,” he said.
That means keeping pediatrics in mind from the beginning of development of the adult program and thinking about the potential therapeutic benefit of the drug in children based on the mechanism of action, disease progression, and its role as part of a therapeutic regimen.
Some of the early development considerations include defining the relevant pediatric populations and ages, whether the pediatric condition would be identical to the adult condition, realistic approaches for collecting data, and potential areas where extrapolation of data is feasible, such as from other indications or age ranges.
Consider the landscape
Regulatory precedence provides an essential baseline of information before a regulatory submission, but it is not the whole picture, explained Kimberly Belsky, executive director for regulatory policy and intelligence and advertising and promotion at Mallinckrodt Pharmaceuticals. Belsky also serves on the RAPS Board.
She urged sponsors to dig into public information, including Summary of Product Characteristics and Pediatric Investigation Plan opinions from EMA, approval letters and review summaries from FDA, clinical trial registries around the world, and press releases.
“But the context of these approvals is key,” Belsky said. “How current is current precedent? Is 5 years ago current?”
The context is going to depend on landscape changes including regulatory revisions, new approvals, and advancements in identification of the disease and treating it, she said. Proceed with caution, Belsky said, because some of this contextual data may be confidential information that sponsors won’t be able to access.
Clinical study design considerations
Clinical study design is another area where sponsors can potentially run into problems, Huemer said.
It is important to determine the number of patients, their location, pediatric-specific endpoints (including patient-reported outcomes), potential benefit and acceptability to patients and families, as well as technical limitations.
“Please consider involving parents, caregivers, and older children. This is really important to get to the point to show a benefit,” Huemer said.
RAPS Convergence 2021 presentation


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