Paediatric excipient risk assessment (PERA) tool and application for selecting appropriate excipients for paediatric dosage forms – Part 2

Abstract

It is necessary to use a scientifically sound process for excipient risk evaluation, selection, and management in order to develop paediatric medicinal products that are both safe and effective. The “Paediatric Excipient Risk Assessment (PERA)” framework, which proposes a comprehensive approach by considering all relevant factors related to patient, dosage form, and excipient attributes, was developed and published as part 1 of this paper series, to enable the rational selection of excipients for paediatric medicinal products. This article is Part 2 of the series and presents the PERA tool that allows easy adoption of the PERA framework. Using a straightforward heat map scoring approach (Red, Yellow, and Green category) for risk evaluation, the PERA tool can be used to compare and choose excipients. The PERA tool will help users identify potential gaps in excipients information that will help with risk-based mitigation planning. Several case studies covering frequently used and novel excipients for oral, as well as the choice of excipient for parenteral products for neonatal administration, serve to illustrate the PERA tool’s usefulness.

Introduction

Age-appropriate formulations are required to deliver pharmaceutical actives safely and efficaciously to patients aged < 18 years of age. This has been reinforced in both the United States (US) and European Union (EU) via guidelines that require consideration of the formulation in the paediatric study plan (PSP) and paediatric investigation plan (PIP), respectively [1],[2],[3], [4], [5]. Pharmaceutical excipients are required to enable suitable, acceptable, and stable dosage forms to be formulated [6]. Whilst a scientifically sound process for excipient selection is required for any formulation, additional factors need to be considered when selecting appropriate excipients for paediatric formulations. Accordingly, a systematic risk–benefit assessment process called the “Paediatric Excipient Risk Assessment (PERA)” framework was developed as reported in Part 1 of this series of papers (Fig. 1). The PERA Framework enhances the objectivity and transparency of the decision-making process by providing a structured and systematic risk–benefit assessment approach that could be adopted by both companies and regulatory agencies. Part 1 of the publication also highlights current resources available on excipients for paediatric products, common practices used in the industry, regulatory guidance and knowledge gaps.

The current paper (Part 2 of the publication) presents a risk–benefit analysis tool developed using the PERA framework to systematically document the analysis for a particular excipient or multiple excipient options with similar functionality to enable decision-making using the PERA principles. Several case studies are presented to demonstrate the use of the PERA framework and tool to facilitate adoption of the tool by users.

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Table 3: Preliminary formulations for the oral minitablet sprinkle dosage form for case study 1.

Anjali Agrawal, Smita Salunke, Alfred Rumondor, Karen Thompson, Grazia Caivano, Jennifer Walsh, Brian Enright, Philip Sherratt, Kevin Hughes, David Clapham, Peter Kuehl, Paediatric excipient risk assessment (PERA) tool and application for selecting appropriate excipients for paediatric dosage forms – Part 2, European Journal of Pharmaceutics and Biopharmaceutics, 2024, 114447, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2024.114447.

See also the article on the first part

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