The US Food and Drug Administration (FDA) issued final guidance to assist sponsors in developing anti-infective drugs for the pediatric population. The guidance provides recommendations for developing anti-infective drugs, including antibacterials, antifungals, and antiparasitic products, for pediatric populations.
 

Drug Product Development Considerations

Sponsors should consider the following when developing anti-infective drug products for the pediatric population:

(1) Efficacy extrapolation:

(1.1) Efficacy results from adequate and well-controlled clinical trials in adult participants can be extrapolated to a pediatric patient population if:

(1.1.1) The course of the infectious disease is similar in adult and pediatric populations. This implies a similar disease process, including the organisms recovered from the site of infection.

(1.1.2) The effects of the drug product are sufficiently similar in adult and pediatric populations.

(1.2) For infections in which the pathophysiology and clinical manifestations of the disease are different between adult and pediatric populations or between the different subgroups in the pediatric population, reliance solely on efficacy demonstrated in adult participants may not be appropriate. 

(1.2.1) When efficacy cannot be extrapolated from adult or older pediatric populations to younger pediatric populations, adequate and well-controlled clinical trials may be needed to support the indication

(2) Cohorts based on age, body weight or body surface area:

(2.1) Phase 3 clinical trials in adult participants should include adolescent participants (12 years and older) when there are sufficient safety data from adults to assess the risks and the prospect of direct benefit for the adolescent participants. Where appropriate from a scientific and ethical perspective, FDA strongly encourages sponsors to enroll adolescent participants in adult trials.

(2.2) Cohorts for pediatric studies should be determined based on the incidence of the disease and any specific considerations for the drug product under evaluation, such as factors that may influence pharmacokinetics or safety. FDA encourages enrollment of some age cohorts in parallel rather than in sequence for drug products that do not have specific safety concerns or pharmacokinetic (PK) properties that warrant a sequential approach. 

(2.3) Neonates present challenges for dosing considerations to achieve drug exposures required for efficacy and to assess exposures associated with toxicities.

(2.4) The sponsor should consider the need to assess the effect of obesity on dose selection.

(3) Safety data:

(3.1) In general, the sponsor should collect safety data using the intended dose and duration of use of the drug product.

(3.2) In cases where an anti-infective drug is being developed for a pediatric-specific Indication, FDA recommends that sponsors provide supportive safety and efficacy data if available from adult participants with a related indication (e.g., acute bacterial sinusitis). Sponsors should discuss their development plans with the Agency.

(3.3) Safety data from nonclinical studies, known safety signals from the drug class, and the safety profile in adults can provide supportive information and identify adverse events of interest for evaluation in pediatric studies. However, certain toxicities may affect developmentally immature organ systems and tissues that are unique to the pediatric population, with increasing risk likely with decreasing age. These situations may merit additional safety assessments.

(3.4) The size of the recommended pediatric safety database of a drug product depends on several considerations in addition to those noted above, including the incidence of the disease, adverse event profile of the drug product or drug class, and expected use of the drug product in the pediatric population. Sponsors should discuss the size of the safety database with the Agency as the clinical development of the drug product proceeds.

(3.5) In general, pediatric studies of anti-infective drug products use an active comparator that is considered standard of care (SoC) at the trial site and may include different comparators at different trial sites. In these trials, treatment allocation with unequal randomization with more subjects in the experimental arm versus SoC is acceptable.

(3.6) Safety data from a comparative pediatric study (e.g., new drug product versus SoC) maybe needed for a drug product with limited data (e.g., a new drug class) or concerning findings (e.g., toxicity findings in nonclinical studies).

(3.7) Although comparative safety data are more interpretable, if appropriate from a regulatory perspective, a non-comparative study may be considered acceptable for a drug product in a known class with a well-characterized safety profile in adults and children.

(3.8) If the dose and duration of treatment are similar across different indications, the sponsor can use safety data from one indication to support the safety data for other indications.