The U.S. Food and Drug Administration (FDA) has recently published a guidance on neonatal clinical pharmacology studies.
This guidance is intended to assist sponsors of investigational new drug applications (INDs) as well as applicants of new drug applications (NDAs), biologics license applications (BLAs), and supplements who are planning to conduct clinical studies in neonatal populations.
Given that most drugs used in neonatal intensive care units (NICUs) are off-label, it is of great importance for such drugs information be obtained in neonates in order to better address gaps in their labeling process. In addition, therapies should be developed for conditions unique to neonates.
Effectiveness, safety, or dose-finding studies in neonates involve assessing clinical pharmacology information, such as information regarding a product’s pharmacokinetics (PK) and pharmacodynamics (PD) to advise on dose selection. According to this guidance, before initiating neonatal clinical pharmacology studies, the sponsor should assess the available scientific information regarding the mechanism of action of the drug, the PK of the drug, and the ontogeny of any organs and tissues that are involved in the predicted response to the drug or its metabolites. This scientific information can be derived from several sources, including applicable animal models, in vitro studies, and other potentially relevant clinical studies. Furthermore, such scientific knowledge could be used to develop models and perform simulations focused on neonatal clinical pharmacology studies.
Moreover, due to neonates developmental and growth considerations it should be recommended to follow any specific drug given to neonates for potential safety issues longer than for older children and adults. While long-term endpoints could be recommended to assess the safety and efficacy of drugs administered in the neonatal period, it is also important to develop short-term endpoints where feasible.
The general considerations described in this guidance apply also to any neonatal studies that include clinical pharmacology assessments.
More details of this guidance are available here.