Global Pediatric Development of Drugs, Biologics, and Medical Devices
vii
Foreword
Over the last 20 years, pediatric drug development has advanced from routine exclusion of pediatric
patients from clinical trials to early consideration of pediatric studies during adult development when
used in pediatric patients is anticipated.
The transforming legislation passed, including in the US, the Food and Drug Administration
Modernization Act (FDAMA) in 1997, Best Pharmaceuticals for Children Act (BPCA) in 2002, and Pediatric
Research Equity Act (PREA) in 2003, and then in the European Union (EU), the Paediatric Regulation in
2006, has led to this change in paradigm. Based on data collected since the implementation of the legal
framework in the US and from the first 10 years of the EU Paediatric Regulation, these initiatives have
been successful in increasing the availability of approved therapies for pediatric patients.
However, pediatric drug development raises recognized specific challenges. For example, devel-
opmental changes may require specific investigations in specific age or weight groups, different safety
considerations, the need for pediatric‐specific endpoints and formulations, and the need to incorporate
specific research protection. As a result, substantial gaps remain in the therapies available, and it is becom-
ing clear that legislation may act as an enabler but cannot substitute the inherent research challenges that
affect product development.
Therefore, the regulatory agencies have put forth much effort in recent years to achieve global reg-
ulatory collaboration and harmonization, which have been helpful in mitigating these challenges. Since
2014, international experts have been convening to revise the International Council for Harmonisation
of Technical Requirements for Pharmaceuticals for Human Use (ICH) E11 Guideline on Clinical
Investigations of Medicinal Products in Pediatric Populations and generate new pediatric-specific guide-
lines, such as for pediatric extrapolation. ICH also created a pediatric standing group. These initiatives
strive to reduce substantial differences between regions in accepting data for global pediatric medicine
development programs. In addition, there are other activities focused on more targeted harmoniza-
tion at the product or therapeutic level. For example, there are monthly teleconferences among FDA,
European Medicines Agency, Health Canada, Pharmaceuticals and Medical Devices Agency in Japan,
and Therapeutic Goods Administration in Australia to exchange evolving science and discuss the current
regulatory approaches for specific product applications in pediatrics.
Pediatric medical devices suffer from significant challenges as well. Despite specific legislation to
encourage medical device development (such as the Pediatric Medical Device Safety and Improvement Act
and 21st Century Cures Act), children have always lagged adults when it concerns regulatory approval of
innovative medical devices. In the past decade, less than one-quarter of medical devices receiving regu-
latory approval (either premarket approval or humanitarian device exemptions) were for pediatric use.
Several challenges impede device development in children, including:
• Difficulty in conducting safety and efficacy studies in small and heterogeneous pediatric populations
• Ethical considerations testing devices which may carry a perception of safety-related liability
vii
Foreword
Over the last 20 years, pediatric drug development has advanced from routine exclusion of pediatric
patients from clinical trials to early consideration of pediatric studies during adult development when
used in pediatric patients is anticipated.
The transforming legislation passed, including in the US, the Food and Drug Administration
Modernization Act (FDAMA) in 1997, Best Pharmaceuticals for Children Act (BPCA) in 2002, and Pediatric
Research Equity Act (PREA) in 2003, and then in the European Union (EU), the Paediatric Regulation in
2006, has led to this change in paradigm. Based on data collected since the implementation of the legal
framework in the US and from the first 10 years of the EU Paediatric Regulation, these initiatives have
been successful in increasing the availability of approved therapies for pediatric patients.
However, pediatric drug development raises recognized specific challenges. For example, devel-
opmental changes may require specific investigations in specific age or weight groups, different safety
considerations, the need for pediatric‐specific endpoints and formulations, and the need to incorporate
specific research protection. As a result, substantial gaps remain in the therapies available, and it is becom-
ing clear that legislation may act as an enabler but cannot substitute the inherent research challenges that
affect product development.
Therefore, the regulatory agencies have put forth much effort in recent years to achieve global reg-
ulatory collaboration and harmonization, which have been helpful in mitigating these challenges. Since
2014, international experts have been convening to revise the International Council for Harmonisation
of Technical Requirements for Pharmaceuticals for Human Use (ICH) E11 Guideline on Clinical
Investigations of Medicinal Products in Pediatric Populations and generate new pediatric-specific guide-
lines, such as for pediatric extrapolation. ICH also created a pediatric standing group. These initiatives
strive to reduce substantial differences between regions in accepting data for global pediatric medicine
development programs. In addition, there are other activities focused on more targeted harmoniza-
tion at the product or therapeutic level. For example, there are monthly teleconferences among FDA,
European Medicines Agency, Health Canada, Pharmaceuticals and Medical Devices Agency in Japan,
and Therapeutic Goods Administration in Australia to exchange evolving science and discuss the current
regulatory approaches for specific product applications in pediatrics.
Pediatric medical devices suffer from significant challenges as well. Despite specific legislation to
encourage medical device development (such as the Pediatric Medical Device Safety and Improvement Act
and 21st Century Cures Act), children have always lagged adults when it concerns regulatory approval of
innovative medical devices. In the past decade, less than one-quarter of medical devices receiving regu-
latory approval (either premarket approval or humanitarian device exemptions) were for pediatric use.
Several challenges impede device development in children, including:
• Difficulty in conducting safety and efficacy studies in small and heterogeneous pediatric populations
• Ethical considerations testing devices which may carry a perception of safety-related liability