Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Exploring Paediatric Indications for Off-patent Drug Substances - Strategic Input of Regulatory Affairs ***

Dr. Michael Berntgen (Abschlußjahr: 2003)

Summary

The issue of the lack of information on the paediatric use of drug substances is commonly known. Various investigations have shown that paediatric treatment suffers to a great extent from off-label and/or unlicensed use of medicinal products. Typical drug classes are analgesics, antibiotics, and bronchodilatators. The situation gets worse especially in critically ill patients like newborns in an ICU setting, but is also of significant interest in general practice.

A variety of off-patent drug substances with a long history of medical use is affected by this issue. However, as these medicinal products face generic competition, stimulation of their paediatric development requires special initiatives. The current European regulatory environment provides in general no incentives through protection rights for the exploration of e.g. new indications of off-patent drug substances. The recent proposals of the 'Review 2001' regarding the amendment of the regulatory environment also offer no improvement of this situation. Development of off-patent drug substances is hence a general issue in the EU.

Regarding paediatric development the use of the framework for orphan medicinal products could be an option. Under its criteria for an orphan drug designation this system may offer market exclusivity as an incentive as well as further advantages. However, as this regulatory framework is exclusively applicable to rare conditions that are life-threatening or serious / debilitating it may not be applicable to the issue of the lack of paediatric data in general.

In the US exist a lot of experience with initiatives to stimulate paediatric development. Recent evolutions specifically address the aspects of off-patent drug substances. This system is complementary to other initiatives applicable to on-patent drug substances.

Discussions on the creation of a new European legislation for paediatric medicinal products have already been started. The current proposals consist of two separate regulations for on-patent and off-patent drug substances. In general, the experiences with the US programmes as well as the framework for orphan medicinal products represent the basis of these proposals. The paediatric development of off-patent drug substances shall be stimulated by the creation of a paediatric marketing authorisation and the establishment of a study fund.

With respect to the registration of paediatric use of medicinal products special attention needs to be paid on the various sources of medical data for off-patent drug substances. This is of utmost need as the avoidance of any unnecessary trials in the paediatric population is generally required. Flexibility of both industry and authority is requested to handle this matter adequately. Moreover, it is acknowledged that a high level of clinical excellence is required. The use of available structures for networking and expert consultation is recommended.

The master thesis offers an up-to-date compilation of the regulatory aspects to be considered for a strategic decision on a paediatric development plan for an off-patent drug substance. An assessment of the planned regulatory initiatives in the EU in terms of their stimulation of paediatric development is made. The impact of US labelling changes from paediatric exclusivity programmes on EU product information is analysed. Key aspects of the data necessary for registration are highlighted under consideration of the off-patent setting. Special emphasise is laid on already existing clinical networks and respective examples are given. In conclusion, an individual assessment for each drug substance is required to decide upon the investment into a paediatric development as it could be an interesting opportunity for both the company and the medical society due to the evoluting regulatory framework.

Pages: 38