Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory strategies for life-cycle management of chemical defined cytostatic drugs with regard to the new pharmaceutical legislation ***

Dr. Karen Rosenkranz (Abschlußjahr: 2005)

A number of new regulations, directives and corresponding guidelines have been revised within the last years and a few more will be coming soon. So that regulatory environment is becoming more and more complex. Moreover, with an expanded EU with its different national positions does not make the regulatory work in a multinational operating company much easier. Against this background developing regulatory strategies for product life-cycle management is becoming more and more essential to improve the return of investment. Therefore, the pharmaceutical company might establish an effective life-cycle management team. In addition to regulatory affairs, key personnel from the following departments should be considered for inclusion in the team: e.g. R&D, patent counsel, manufacturing, marketing, licensing, and perhaps someone in the upper management.

The framework of this master thesis is intended to evaluate the assets and drawbacks of the regulatory strategies for life-cycle management of chemical defined cytostatic drugs in a multinational operating company. With the focus on the recent reform of the pharmaceutical legislation, regulatory life-cycle strategies for a NCE in an early life-cycle stage and for an established product in the late life-cycle stage are exemplified with case studies. Beside, the impact of forthcoming legislations is also evaluated briefly.

With regard to a fictive case scenario for a NCE the appropriate application procedure (taking into account the new procedures as well) and future strategies for further developments of the product are evaluated. For the selection of the application procedure the company has to take various details into consideration like time to market, number of countries involved, future handling of variations, fees as wells as the period of data and market exclusivity. With regard to all these details the CP with the accelerated assessment procedure as proposed under the new Regulation (EC) 726/2004 seems to be the right choice. In comparison to the previous 10-year data and market exclusivity granted for CAP, in the future for all new products only an eight-year data exclusivity and a 10-year market exclusivity will be granted according to the 8 + 2 + 1 formula. An extension of the period of exclusivity by one additional year will be only granted when a new indication is obtained during the first eight years of the MA.

For further developments the new draft regulation on Medicinal Products for Paediatric Use, should be taken into consideration when the original product is protected either by a SPC or by a patent, which qualifies for granting the SPC. According to this draft regulation a paediatric investigation plan shall become an integral part for a new drug application as well as for further developments. Moreover, the MAH should undertake first steps in the direction of the implementation of the eCTD, like the implementation of a document management system.

In the second case scenario life-cycle strategies for an established product are analysed. Even for those national approved products it could be one objective to simply the work of maintenance through harmonisation of the quality part of the dossier or renewal dates. A harmonised quality part of the dossier might be achieved through a set of co-ordinated variations covered in an update of this dossier part. Thus, would not only alleviate the regulatory workload or the workload at the manufacturing site, i.e. not take note of different shelf life specifications or batch sizes, but would also reduce the overall costs in the economic sense. Moreover, the required documentation of future developments could be assessed and assembled more easily. Subsequently, the harmonisation of the renewal dates could be carried out in order to reduce the amount of PSURs, which now have to be issued for each national renewal. Moreover, when the text of the new legislation comes into force, the intervals of submission of a PSUR will have been shortened from five to three years. As a counter move, the renewals for products older than five years will be ceased and the MA will become valid for an unlimited period.

All in all the new legislation promises shorter times to approval and the new CG may help to prevent a referral at the of the MRP or DCP. However, up to now exact details of the new application procedures and their enforcement are missing. One drawback is the introduction of the concept of one global MA deteriorating the protection of further developments of the product. In order to cope with the new regulatory environment the MAH has to design a tight life-cycle management plan long before approval to ensure an early submission before the periods of data and market exclusivity are expired. Another option might be to protect further developments of the products like new pharmaceuticals forms by a patent. It would be also conceivable if no protection of further developments of the product could be obtained like patent or extension of the period of data market exclusivity, the MAH might avoid the investment, and thus could be preventing research for innovation.

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