A review of the experience with pediatric written requests issued for oncology drug products

Akalu, Alemayehu; Meng, Xi; Reaman, Gregory H.; Ma, Lian; Yuan, Weishi; Ye, Jingjing

doi:10.1002/pbc.28828

Cited by 17 publications

(11 citation statements)

References 4 publications

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“…Future studies should investigate if products exempted from the US PREA received a waiver in the EU, which could explain the low number of discrepancies in guidance for pediatric use between the SmPC and the USPI; Or if pediatric requirements were posted by the EMA regulators, this led to a request for voluntary pediatric drug development through BPCA in the US (spillover effect). However, one study found that of the 40 Written Request issued through US BPCA for oncology products since 2001, only three products have been approved for use in the pediatric population [ 29 ] suggesting that the US BPCA only provide a small contribution to the aligned guidance for pediatric use for oncology products found in our study.…”

Section: Discussionmentioning

confidence: 71%

Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

et al. 2022

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Pediatric legislations in the European Union (EU) and the United States (US) have increased medicines approved for use in the pediatric population. Despite many similarities between these frameworks, the EU Paediatric Regulation more often provides regulators with a mandate to require pediatric drug development for novel medicinal products compared to US regulators. If used, this could give rise to differences in the guidance for pediatric use provided for clinicians in the two regions. However, the level of discordance in the guidance for pediatric use between the two regions is unknown. This cross-sectional study compares guidance for pediatric use in the EU Summary of Product Characteristics (SmPC) and the US Prescription Information (USPI) on the level of indications granted for novel medicinal products approved after the pediatric legislations came in to force in both regions. For all indications granted as of March 2020 for novel medicinal products approved in both regions between 2010 and 2018, we compared the guidance for pediatric use in the EU SmPC and the USPI. The guidance for pediatric use differed for 18% (61/348) of the listed indications covering 21% (45/217) of the products, but without the guidance being contradictory. Where guidance differed, an equal share was observed for indications with a higher level of information for pediatric use in one region over the other (49% (30/61) in the US; 51% (31/61) in the EU). The discrepancies in pediatric information could be explained by differences in regulations for 21% (13/61) of the indications. Only a few conditions and diseases (EU n = 4; US n = 1) were observed to cover potential pediatric use outside the approved adult indication. Although the EU Paediatric Regulation more often provides regulators a mandate for requiring pediatric drug development as compared to the US PREA, this was not reflected in the prescription information approved by the two regulatory authorities.

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Section: Discussionmentioning

confidence: 71%

Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

et al. 2022

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“…The orphan drug legislation provides incentives to develop drugs to prevent, diagnose, or treat rare diseases and conditions, including in pediatric patients. The US BPCA has been shown as the predominant policy contributing to pediatric drug development for cancer drugs in the US ( 25 ). This development is important as many of the drugs exempted by the US PREA have been shown to have a mechanism of action warranting pediatric development plans ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Mandatory requirements for pediatric drug development in the EU and the US for novel drugs—A comparative study

2022

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Mandatory pediatric legislation has been implemented in the European Union (EU) and the United States (US) to increase research and the availability of drugs for the pediatric population. Differences in the legislative framework can cause different pediatric requirements for similar indications granted for similar drugs across jurisdictions. This cross-sectional study compares the pediatric requirements for therapeutic indications granted at the time of initial approval for novel drugs approved in the two regions from 2010 to 2018. We collected the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) decisions to grant a waiver and/or to agree on a pediatric development plan and deferrals hereof at marketing authorization (MA) from publicly available documents. An agreed pediatric development plan was required for 66% (N = 188/285) and 63% (N = 134/212) of the indications granted in the EU and the US at the time of approval, respectively. Almost all (EU; 98%, US; 89%) were deferred until after MA. Based on the broad scope of the EU Pediatric Regulation, an additional 36 PIPs originated from the indications granted at MA. In the subset of indications granted for drugs approved in both the EU and the US (N = 232), significantly more indications resulted in an agreed pediatric development plan for one or more subsets of the pediatric population in the EU (N = 185) as compared to the US (N = 82). This was based on the exemption of orphan designated drugs in the US and the broader scope of the EU Pediatric Regulation. However, indications subject to the mandatory pediatric legislation in both regions (N = 131) most often had similar regulatory requirements for the inclusion of the pediatric population from the EMA and the US FDA (83%, N = 109). In conclusion, when comparing mandatory pediatric requirements, more pediatric development plans were agreed upon in the EU than in the US, in line with the broader mandates of the EU Pediatric Regulation. However, authorities most often had similar regulatory requirements when an indication was subject to pediatric legislation in both regions.

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“…5 The US Food and Drug Administration (FDA) has also enacted key pieces of paediatric-focused legislation: the Best Pharmaceuticals for Children Act (BPCA) issued in 1997 contained economic incentives for conducting paediatric studies of drugs and biological products; the FDA Written Request component of the BPCA and the Research to Accelerated Cures and Equity (RACE) for Children Act have resulted in numerous approvals of childhood cancer drugs. [16][17][18] Additionally, on the basis of the Paediatric Research Equity Act (PREA), which requires companies to conduct paediatric trials unless it can be shown conclusively that they are not needed, the FDA was recently authorised to require sponsors to submit an initial Paediatric Study Plan (iPSP) with an original application for oncology products that may target the growth or progression of a paediatric cancer, as of 18 August 2020. Moreover, new therapies with orphan-designated indications will no longer be exempt from PREA.…”

Section: Introductionmentioning

confidence: 99%

Childhood cancer drugs in China: An overview and comparison of regulatory approvals in China and the United States

Zhang

Wagner

Han

et al. 2021

Intl Journal of Cancer

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Different from less developed countries, 80% of children with cancers in the United States are cured. Traditional chemotherapy drugs are the mainstay of therapies; new targeted medications have become available recently. Using publicly available data, we created a database of cancer drugs with paediatric malignancy indications approved by 31 October 2020 in China and the United States. We compared numbers, type, indications and listing on the World Health Organization Model List of Essential Medicines for Children (WHO EMLc) between the two countries, assessed the correlation between paediatric indications and cancer incidences, and described evidence supporting approvals of targeted medications in the two settings. Our study showed that by 31 October 2020, 31 and 39 cancer drugs available in China and the United States were approved for use in children, corresponding to 137 and 102 paediatric cancer indications, respectively. About half of these drugs (17 in China and 18 in the United States) were listed on the WHO EMLc. The correlation between indications and burden of disease was higher in the United States (r = 0.68) than China (r = 0.59). More traditional chemotherapy drugs were approved in China (n = 27) than the United States (n = 19). Of 20 targeted childhood anticancer medicines approved in the United States, mainly on the basis of single arm trials (27/32 indications, 84.4%), only four were approved for paediatric indications in China, at a median of 2.8 years after US Food and Drug Administration approval.A harmonised, evidence-based regulatory framework is needed to ensure approvals of needed, safe and efficacious childhood cancer drugs across the world.

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A review of the experience with pediatric written requests issued for oncology drug products

Cited by 17 publications

References 4 publications

Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

Mandatory requirements for pediatric drug development in the EU and the US for novel drugs—A comparative study

Childhood cancer drugs in China: An overview and comparison of regulatory approvals in China and the United States

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