Significant progress has been made in developing medicines for children since implementation of pediatric legislation in the US (1997) and EU (2006). However, gaps still exist, and regulatory authorities continue to address them.
In August 2017, the US passed the FDA Reauthorization Act and with it the Research to Accelerate Cures and Equity for Children Act (RACE). RACE for Children Act will eliminate exemptions and improve opportunities for cancer drugs to be developed for children by:
Requiring companies developing cancer drugs to do PREA studies in children when the molecular target of their drug is relevant to children's cancer
Ending the exemption of PREA obligations for cancer drugs with orphan designations if the molecular target of the drug is relevant to children's cancer
In August 2018, the FDA will publish a list of molecular targets substantially relevant to growth and progression of pediatric cancer. It will also list molecular targets of new cancer drugs and biological products for which pediatric studies will be automatically waived.
Other positive steps include the following.
Congress reauthorized through 2020 the Rare Pediatric Disease Priority Review Voucher program in the 21st Century Cures legislation.
In the EU, the Commission report on 10 years EU Pediatric Regulation (October 26, 2017) showed encouraging impact of Pediatric Regulation overall, though the Regulation appears most effective when adult and pediatric needs overlap. Fewer advances have been made in diseases that are rare or unique to children. While some instances of over- or under-compensating drug developers with financial rewards exist, overall benefits seem to outweigh costs, and the Regulation appears to be improving pediatric medicine availability.
As a result, the European Commission does not recommend re-opening the legislation at this stage. It will evaluate pediatric and orphan Regulations to better understand their combined effects and why orphan rewards do not seem to be driving pediatric development for rare diseases. Findings are expected to be delivered in 2019, enabling the next Commission to make informed decisions about policy options.
In the meantime, the European Commission and EMA have begun working on measures to streamline application and implementation of the Regulation. This will include changes to deferrals, revisiting the PIP process, and, if needed, adapting corresponding Commission guidelines, multi-stakeholder discussion of pediatric needs, measures to encourage international cooperation, and harmonization.
In respect to deferrals, a revised and revoked class waivers list will come into effect in July 2018 (8 waivers were revoked, 15 updated, and 9 confirmed). From July 2018 on, applications for new medicines or variations of marketing authorization will be validated against this list. Waivers, specifically those in oncology, will no longer be automatic. Regulators will expect companies to have considered product mechanism of action and pediatric needs prior to deciding on them.
Regarding multi-stakeholder discussion of pediatric needs, the EU Commission and EMA held a workshop with patients, academia, healthcare professionals, and industry on March 20, 2018. Potential improvements to implementation of the Regulation (pediatric needs, timely completion of PIPs, processes, expectations for handling them) were discussed. An action plan addressing challenges will be published mid 2018. The EMA, EU Commission, and stakeholders will need to commit to execution of it within two years.
ICH E11 (R1) "Clinical Investigation of Medicinal Products in the Pediatric Population" entered into force in February 2018 and aims to further improve pediatric research globally. Addendum R1 reflects latest thinking in technical, scientific, and regulatory approaches and recognizes key topics where consensus had not been achieved, including:
Ethical considerations
Age classification and pediatric subgroups including neonates
Pediatric formulations
Common scientific approaches to aid discussions in different regions
Pediatric extrapolation and introduction of modeling and simulation
Practicalities in design and execution of pediatric trials, including feasibility, outcome assessments, and ...
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