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Regulatory Focus™ > News Articles > 2020 > 6 > Pediatric anti-infective development addressed by FDA

Pediatric anti-infective development addressed by FDA

Posted 29 June 2020 | By Kari Oakes 

Pediatric anti-infective development addressed by FDA

The US Food and Drug Administration (FDA) has issued new draft guidance for sponsors who are developing anti-infective drug products for the pediatric population.
 
The draft guidance notes that pediatric drug development in general comes with some challenges, including the fact that differences not only in body size but also organ maturation and body fluid composition and distribution can affect drug pharmacokinetics and pharmacodynamics in children. Also, some infectious diseases have different manifestations in neonates and infants. Finally, logistics and ethics may limit the ability for sponsors to obtain certain samples from children.
 
Efficacy for anti-infective in a pediatric population can be extrapolated under the guidance if both of two requirements are met: First, the course of the infectious disease proposed to be treated must be similar in pediatric patients as adults. “This implies a similar disease process, including the pathogens recovered from the site of infection.  Second, the drug’s effect on pediatric patients should be “sufficiently similar” in adults and children.
 
“Even when efficacy can be extrapolated, however, pediatric data will be needed to assess the safety and pharmacokinetics of the drug product,” according to the draft guidance , with the goal of demonstrating that the dosing regimen proposed achieves similar exposure for pediatric patients as for adults.
 
Extrapolation of efficacy will not be possible from adults to children or from one pediatric subpopulation to another when a disease has differing pathophysiology and clinical manifestations in the various subgroups. The draft guidance gives the example of tuberculosis, where the clinical course in adults and older children usually only has pulmonary involvement. In toddler-aged and younger children, though, disseminated disease is more common, so extrapolation of efficacy for a drug to treat tuberculosis would not be possible from older children or adults to those aged 2 years or younger.
 
When making decisions about age cohorts for pediatric studies, disease incidence and drug-specific considerations should be taken into account; weight-based definitions can be used when appropriate.
 
Adolescents aged 12 years and older should be included in adult clinical trials. When scientifically and ethically appropriate, “FDA strongly encourages sponsors to enroll adolescent patients in adult trials,” says the draft guidance.
 
When collecting safety data, sponsors should include all ages for which the drug will be indicated and the intended dose and duration should be used. Adult studies can inform pediatric studies, pointing out adverse events to look for in conducting pediatric studies. The size of a pediatric safety database for a drug “depends on several factors,” including disease prevalence, adverse event profile, and how the drug is expected to be used in pediatric patients. FDA should be consulted “on an ongoing basis” as the drug product is developed, according to the guidance.
 
Finally, “there can be some flexibility in the inclusion and exclusion criteria to identify pediatric patients for enrollment” when studies are primarily intended to evaluate safety and/or pharmacokinetics, says the agency. Also, invasive samples and testing should be minimized where possible in the pediatric population.
 
The guidance was developed by the agency’s Center for Drug Evaluation and Research (CDER), together with the Center for Biologics Evaluation and Research (CBER). The complexity of some CBER-regulated biologic products, such as cellular and gene therapies and phase therapies, “there may be additional development considerations,” noted the guidance, so sponsors should be in touch with the appropriate CBER review division throughout the development process. The draft guidance will be available for public commentary for a 60-day period. 
 
FDA

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