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Building on more than a decade of initiatives to spur pediatric labeling on drugs and biologics, regulatory authorities are bolstering incentives for sponsors to develop more information faster on the use of medicines in children.
Building on more than a decade of initiatives to spur pediatric labeling on drugs and biologics, regulatory authorities are bolstering incentives-and applying more pressure-for sponsors to develop more information faster on the use of medicines in children. The aim is to further narrow the time gap in developing drugs for adults and for young patients.
New European requirements call for sponsors to submit a Pediatric Investigation Plan (PIP) when filing for market authorization. That makes it necessary to consider the design and scope of pediatric studies as early as end of Phase I trials.
In the US, sponsors are not required to submit a pediatric study plan (PSP) at time of filing. FDA reviewers emphasize, however, that they would like to see PSPs at least by the end of Phase II to ensure that pivotal Phase III studies include endpoints that will support pediatric indications. The FDA Safety & Innovation Act of 2012 (FDASIA) made permanent the Pediatric Research Equity Act (PREA), which strengthens policies requiring submission of pediatric assessments. FDASIA also extended study requirements to neonates and included a number of provisions that promote pediatric research and post-approval studies.
Since January 2013, FDA has received 405 PSPs and has “agreed with” almost 200 of them, according to Lynne Yao, acting director of the Division of Pediatric and Maternal Health in the Center for Drug Evaluation and Research’s Office of New Drugs. These and earlier efforts have led to more than 500 pediatric labeling changes, Yao reported at the Drug Information Association’s Pediatric Research Conference in November 2014. She added that FDA permits sponsors to defer pediatric studies, but now is taking stronger action to get promised studies completed on time.
To encourage sponsors to start pediatric studies before submitting an NDA or BLA, FDA is clarifying and encouraging more flexible research approaches. A new draft guidance describes innovative methods for conducting clinical pharmacology studies in pediatric populations and supports use of exposure-response knowledge from relevant prior adult trials [General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products,” Dec. 9, 2014 at fda.gov]. FDA also seeks to spur research in neonates, which are often omitted from general pediatric development programs. Yao acknowledged that it’s particularly difficult to encourage studies in conditions that affect only children.
In addition to stronger study requirements, FDASIA expands market incentives for conducting pediatric trials. The legislation also made permanent the Best Pharmaceuticals for Children Act (BPCA), which extends exclusivity for products studied further to support pediatric labeling. Since 1998, sponsors have qualified for added exclusivity on more than 200 products due to BPCA, Yao reported.
In addition, the legislation encourages development of treatments for rare pediatric diseases by offering priority review vouchers to sponsors of such therapies. The first voucher was awarded under this program in February 2014, authorizing a speedy review of another new drug to the voucher holder. And recent guidance [Rare Pediatric Disease Priority Review Vouchers, Nov. 17, 2014, available at FDA.gov] supports the program by clarifying participation procedures and post-approval reporting requirements.
Development of more pediatric-specific endpoints and biomarkers also promise to streamline pediatric studies. And several pharma companies are collaborating with academics and clinicians to establish a global pediatric clinical trial network, as outlined at the DIA conference. The initiative would relieve sponsors of the need to identify sites and investigators for each research project and would support studies from multiple companies. The envisioned network would identify patients of all ages, from neonates to young adults, in all therapeutic areas and all regions of the world, starting with the US, the United Kingdom and Canada.
Regular consultations among regulatory authorities aim to further harmonize research policies and approval approaches standards for pediatric studies. Such efforts by the “Pediatric Cluster,” which includes regulatory authorities from Europe, Canada, Japan and Australia, aim to avoid unnecessary and duplicative pediatric trials whenever possible. The group discusses general and product-specific topics and issues “commentaries” to sponsors on pediatric research plans submitted to both FDA and the European Medicines Agency (EMA), explained Jean Teaneck, supervisor of the international team in FDA’s Office of Pediatric Therapeutics. Such commentaries are not binding, but aim to facilitate worldwide approval of pediatric indications. In May 2014, FDA and EMA issued a joint proposal for investigating new medicines for Gaucher disease in children, which aims to include children in studies as scientists develop new treatments for this rare condition.