FDA Announces Availability of the Draft Guidance “General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products”

FDA Announces Availability of the Draft Guidance “General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products”

On July 31, 2019, the U.S. Food and Drug Administration (FDA) announced the availability of a draft guidance for industry entitled "General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products."

This draft guidance supplements the FDA draft guidance entitled "General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products" (December 2014), as it addresses general clinical pharmacology considerations in neonates, a pediatric subpopulation. This is the first FDA guidance to focus solely on neonates, defined as the day of birth plus 27 days for full term infants and as the day of birth through the expected date of delivery plus 27 days for preterm infants. It is intended to assist sponsors of new drug applications (NDAs), biologics license applications (BLAs), and supplements who are planning to conduct clinical studies in neonatal populations. The issuance of this draft guidance is required under section 505(d)(2) of the FDA Reauthorization Act of 2017 (FDARA).

Most drugs used in neonatal intensive care units (NICUs) are used in an off-label capacity, therefore it is important that drug studies be conducted in neonates to address gaps in pediatric labeling information. New therapies also need to be developed for conditions unique to neonates. During in utero development, there are significant physiological changes in the fetus involving the normal expression and maturation of organs and tissues including enzyme systems, receptors, transporters, and neurotransmitters. Once fetal development is interrupted by preterm delivery, the normal developmental trajectory of these systems is altered based on the physiological changes that occur after birth. Postnatal development can also be adversely affected by concurrent illnesses, resulting in altered maturation of organs and tissues and affecting the systems responsible for product absorption, distribution, metabolism, and excretion (ADME). These factors can alter the pharmacokinetic (PK; exposure) and pharmacodynamic (PD; response) characteristics of a drug, which are essential components of the clinical pharmacology assessment. 

This guidance addresses general PK, PD, and study design considerations in planning and conduct of neonatal clinical pharmacology studies. Adequate characterization of the PK of a drug can help to optimize dose selection for neonatal studies. Sponsors should collect and analyze both PK and whenever possible, PD data in neonatal studies to determine how the two are linked with respect to exposure-response (E-R). If there are pharmacogenetic differences that affect the PK, efficacy, and safety of a drug in older children and adults, pharmacogenetic analysis is recommended in neonates. In addition, the guidance describes considerations for specific trial design elements when developing a neonatal study plan, including study population and neonatal subgroup classification (based on post-menstrual age [PMA] and postnatal age [PNA]), dose selection, formulation, sample size, blood sampling, and bioanalytical methods.

The "General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products" draft guidance is available at https://go.usa.gov/xyMVu. Please refer to the draft guidance for more details. Additionally, please refer to the FDA in Brief article at https://go.usa.gov/xyMGQ highlighting the FDA’s commitment to gaining more information on the safety and efficacy of existing therapies given to our youngest patients. FDA is publishing this draft guidance to collect additional public comments. You may submit your comments regarding the draft guidance to the docket (Docket No. 2019-16375) available at https://www.regulations.gov up to 90 days following publication in the FEDERAL REGISTER. This draft guidance, when finalized, will represent the current thinking of the FDA on this topic. It does not establish any rights for any person and is not binding on FDA or the public. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience and make your voice count.