FDA guidance for developing paediatric ARVs: online for comment (2018)

Polly Clayden, HIV i-Base

The US Food and Drug Administration (FDA) has published draft guidance on the development of products for treatment of HIV in paediatrics (birth to younger than 17 years of age).

The guidance includes recommendations for sponsors on when to start paediatric formulation development and begin paediatric studies to evaluate new antiretrovirals for the treatment of HIV.

The draft recommendations are summarised as follows:

  • As dosing recommendations for antiretrovirals have consistently been the same for adults and adolescents (12–17 years old), sponsors should include adolescents in phase 3 trials, or should conduct a separate adolescent study in parallel with the adult phase 3 trials.
  • Paediatric formulation development should begin as soon as the adult dose is selected – based on results from the phase 2 trial(s).
  • For infants and children age 4 weeks to less than 12 years, sponsors should enrol cohorts within clinical studies in parallel rather than in sequence, unless a drug has a specific safety or drug disposition factor that requires a different approach. Sponsors can use pharmacokinetic (PK) modelling using the adult and adolescent data for initial dose selection to start parallel enrolment of cohorts across the different weight bands.
  • Cohort enrolment and dose selection during the clinical studies in infants and children should be based on weight rather than age. The selected weight-bands should align with those predefined by the WHO.
  • Approval of a new paediatric formulation (eg granules instead of solution), when safety and PK in children have already been studied using a previously approved formulation, may be supported by a bioavailability/bioequivalence study in adults that show that bioavailability of the two formulations is comparable. If it is not comparable, one or more of the following may be needed to support approval: dose adjustments, scientific rationale to support the difference in bioavailability, or an additional trial. Alternatively, additional work for the development of different formulations might be needed.
  • FDA encourages sponsors to have early discussions with WHO, NGOs, FDA and others on their development plans for paediatrics to meet the needs of infants, children and adolescents with HIV eg selection of formulation, strengths and dosage of a drug.

The FDA invites the submission of either electronic or written comments on the draft guidance by 13 July 2018, before it begins work on the final version.


These recommendations are excellent – notably the alignment with WHO requirements and parallel rather than sequential cohorts.


Pediatric HIV infection: drug development for treatment. Guidance for industry. 14 May 2018.

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