Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Medicinal Products for Nebulisation in Europe: Requirements, Challenges and Options ***

Verena Prusinovsky (Abschlußjahr: 2013)

Summary

Language: English

Inhalation therapy is the most important pillar of disease management for patients suffering from respiratory diseases. Different pharmaceutical forms using different types of administration devices are available and are subsumed under the term “Orally Inhaled Products (OIPs)”. Medicinal products for nebulisation represent one type of inhalation products using a nebuliser for drug administration.

The objective of this master thesis is to highlight the specific aspects associated with medicinal products for nebulisation. Interchangeability of drug and device, co-medication, and the reliability of drug administration in general are important topics which are discussed in the context of nebulisation products.

Moreover, it is intended to provide a general survey about nebuliser based therapy. This encompasses the description of different types of nebulisers like jet-, ultrasonic- and membrane- nebuliser with their specific functionality.

Pulmonary deposition is highly dependent on the aerosol quality. For this reason comprehensive aerosol characterisation constitutes an essential part in the development of medicinal products for nebulisation and is predictive on therapeutic efficiency and clinical relevance. This is reflected by  the comprehensive legal framework for quality assessment of nebulisation products in Europe. In particular the monograph 2.9.44 of the European Pharmacopoeia provides guidance specific for the characterisation of nebulisation products which is based primarily on the detailed description of the aerosol pattern and the assessment of the aerosol performance by impactor measurement or laser  diffractometry.

The regulatory requirements for nebuliser products in Europe with regard to the clinical development are illustrated by using the example of the clinical program for a nebulised antibiotic indicated for cystic fibrosis patients.

Different regulatory approaches for a generic/hybrid marketing authorisation are possible and the  selection of the most appropriate strategy constitutes a challenging regulatory task. Inhalation products are categorised as locally acting products. For this reason the usual way to demonstrate equivalence between the generic medicinal product and its reference medicinal product by the conduct of bio-availability studies is not feasible. Specific regulatory guidance and common practice recommend a stepwise approach for the generation of data suitable to support generic marketing authorisations of medicinal products for nebulisation.

Various challenges, the development of medicinal products for nebulisation entails, are identified and possible improvements which could be provided by meeting these challenges are discussed. Different fields of research like tailored drug-device combinations, the development of formulations suitable for nebulisation and improvements of inhalation technique and adherence to therapy are pathways worth to be further pursued. Finally promising new therapy approaches and drug candidates for nebulisation are mentioned using examples from current development.

Considering the various possibilities and also the limitations associated with one specific form of  inhalation therapy no single inhalation platform promoting one type of device or one type of formulation can address all the specific requirements of an optimised therapy. The different aspects  in the context of nebuliser based therapy highlight the fact that medicinal products for nebulisation are high-value niche products which are essential and are the mainstay of inhalation therapy for the target patient population.

Pages 53, No annexes