Work package 13: Regulatory Interactions & Paediatric Development Strategy
Work package leader
Description of the work package
The LENA project has a dual purpose: the acquisition and publication of highly relevant scientific and clinical data and the development of the first orally administered dispersible minitablet of enalapril specifically developed for use in neonates, infants, and children with CHD. Drug development is highly regulated in order to ensure that the development is performed with the necessary rigor to produce data that are suitable for the submission of an application for a Paediatric Use Marketing Authorisation (PUMA).
The work package 13 team of contributors will perform all the tasks at the project level that are required to satisfy the regulatory requirements, while regulatory activities at the study level are part of our Clinical Trial Management Unit. One of the key deliverables will be the Paediatric Investigational Plan (PIP) to be submitted to the Paediatric Committee of the EMA. The PIP will then be discussed with this committee and at the end of the EU grant period a clinical expert report summarizing the data for the PUMA application will be drafted. In order to conduct any studies in humans, an IMPD, the core deliverable of work package 2 on Pharmaceutical Development with extensive input from this work package, and an IB will have to be drafted and regularly updated. Moreover, this WP will ensure that all regulatory demands at the project level, such as adverse event reporting, are carried out as required.
Specifically, during the first 6 months, a critical review of all available clinical data forming the evidence base regarding the pharmacological treatment options for HF in children and of all available data concerning enalapril and its toxicology will be performed. Results of this review will be presented in tables to be used as part of IMPD, IB and PIP. The clinical development plan will be further honed, discussed with all parties involved, and presented as part of the PIP. In addition, the PIP will take into account the information provided in regard to non-clinical safety and pharmacokinetics.
Once the PIP is approved, this work package will closely work with all other work packages in order to ensure that the project and its constituent studies are advanced in line with all regulatory requirements. At the project level, a large part of this effort will be the standardized management and analysis of the data, with the ultimate aim of a joint data analysis to form the foundation for a future PUMA application.
Preparation of this evidence base, the drafting of the paediatric development strategy, and discussions with the regulatory authorities will be led by Ethicare in collaboration with consultancy expertise in experimental medicine, drug development, and paediatric clinical pharmacology. All these tasks will be performed as part of the regulatory packages to high regulatory standards.
The tasks included in work package 13 are described below:
- Creation of the Clinical Investigators’ Brochure (IB) by Dr. Robert Hermann: This task will involve a comprehensive review of all available enalapril data and summary of all project data (e.g. formulation data) followed by collation into an IB which will provide guidance to the clinical investigators.
- Creation and discussion of the Paediatric Investigation Plan by Jenny Walsh, PhD: This work package will take the lead for the creation of the PIP in collaboration with the LENA project participants. The PIP will be submitted to the EMA. The Paediatric Committee of the EMA may ask for amendments, which may require further discussions with the committee and resubmission of an adapted PIP.
- Data summary for future submission of PUMA: As a basis for the creation of Module 2, the summaries of the Common Technical Document (CTD), we will compile all necessary documentation for the future submission of a PUMA application by the commercial partner to be identified in work package 14 on Pharmacoeconomics and Commercialization.