The article provides an overview of the key provisions of the draft guidance documents dedicated to neonatal products. 


The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to considerations for long-term clinical neurodevelopmental safety studies in neonatal product development. Once finalized, the guidance will provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, FDA guidance documents are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance. The present draft guidance is published for public comments – the authority encourages industry representatives to provide their feedback and suggestions to be considered later by the authority. 

infusion pumps

Regulatory Background 

According to the document, it is intended to provide a framework for considering whether and what type of long-term neurologic, sensory and developmental evaluations could be useful to support a determination of the safety of a drug, biological product, or device for use in neonates, and if so, which domains of neurodevelopment may be most applicable. At the same time, the authority also mentions that the matters related to the efficacy or effectiveness assessment of neuroprotective agents are falling outside the scope of the present guidance, while it is primarily focused on the long-term evaluation of neurodevelopmental safety. The document also does not cover the aspects related to toxicity and respective assessment, even though these aspects are important in the context of neonatal product development. With respect to the details of planning clinical trials in neonates and pediatric patients, the authority refers to the appropriate guidance documents dedicated to the said matters, since some of the aspects related to such studies are not addressed in the guidance. It is also explicitly stated that the document does not provide recommendations with respect to neonatal or pediatric safety assessments following studies conducted during pregnancy. 

As explained by the FDA, the current regulatory framework for neonatal and pediatric products is established by the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) as introduced in the Food and Drug Administration Safety and Innovation Act (FDASIA). 

Special Considerations 

First of all, the authority states that the safety and proper performance of products intended to be used in neonates in vitally important since this is a period of critical growth and development. Hence, regular short-term evaluations usually conducted for the products intended for adult patients are not efficient enough in addressing the matters related to the use in neonates due to the potential latent effects. At the same time, the FDA acknowledges that before most of the products used for neonates have not been approved specifically for use in this category of patients, hence, they lack proper evaluation of long-term effects. 

In accordance with the guidance, the parties involved in the development of neonatal products should pay special attention to the potential short- and long-term effects of the respective therapy, irrespective of whether the technology used is entirely new or has been previously used for other patient groups. Sometimes short-term improvement resulting from the therapy could be followed by unexpected long-term harm, thus, the proper assessment of potential long-term risks is required. With respect to the latter, the authority mentions that although there is no universal definition of “long-term”, for the purpose of this guidance, the time frame can be generally thought of as at least 2 years of age or at such time when relevant clinical neurodevelopmental parameters can be reasonably assessed.

Under the general rule, it is important to ensure that any and all products intended to be used in neonates are undergoing a rigorous evaluation addressing the aspects related to dosing, efficacy, or effectiveness, as well as the overall safety for the said group of patients. Some of the matters to be taken into consideration in the context of such assessments are unique for the said patient population, hence, a special approach is required. In this respect, first-in-human studies should be conducted in order to ensure proper evaluation of these aspects, and also to demonstrate long-term neurologic, sensory, and developmental safety. The authority mentions that neonates should also be enrolled in clinical studies for medical products and diagnostic tools initially developed for indications in other populations that will be used for neonates; inclusion of neonates in such studies may be useful to establish design, safety, and efficacy or effectiveness, and these studies may also warrant long-term safety evaluations. 

In summary, the present FDA guidance highlights the key points to be considered with respect to medicinal products intended to be used in neonates in order to ensure safety in the long-term perspective. The document outlines the limitations of using a general approach due to the specifics of such a category of patients and describes the way these specific risks could be addressed. 




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