Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

"Regulations Concerning "Off-Label-Use" of Medicinal Products in Germany" ***

Dr. Angelika Freund (Abschlußjahr: 2004)

In some areas, especially pediatrics, pediatric oncology, and general oncology, the "Off-Label-Use" of medical products has become a very common issue also in Germany.

In order to be able to discuss and eventually solve the problems related to the "Off-Label-Use" issue, it has to be defined what exactly is enclosed in the term "Off-Label-Use". It seems that there are different opinions on how to define the term. This master thesis discusses the key points to be considered for the definition of "Off-Label-Use".

The aim of this master thesis is to show the major problems, arising between the different sectors of the legislation, related to the "Off-Label-Use" of medicinal products in Germany and indicate possible solutions in order to achieve a clearer situation for all parties involved.

A part of the problem does relate to different jurisdiction depending on the different view points of legislation. On the one hand the federal (highest) social court in Germany, based on the current social law, has restricted the "Off-Label-Use", on the account of the public health insurance, to the following cumulative pre-conditions:

It is a life-threating disease for which
No other therapy is available and
Based on the published data there is a justifiable expectation that the therapy with this drug would be effective (palliative or curative).
But on the other hand the upper court of Cologne, based on the criminal law, decided that a doctor is forced to use medicinal products "Off-Label" if the therapy with a certain drug in a certain indication is established within the medicinal community, although it has no marketing authorisation in this indication.

Concerning the German liability law, the doctor is responsible for the treatment respectively non-treatment of his patients and to a certain extend the side effects associated with his action respectively non-action. On the other hand the social law does only allow the treatment on behalf of the public health insurance if it is adequate in the sense of enough, appropriate, and cost-effective. A non-registered drug is, in general, considered by the federal social court as non-adequate, non-appropriate and non-cost-effective. Therefore the public health insurance might refuse to grant payment and initiate a regress against the doctor for such "Off-Label" prescription and legally is allowed to do.

The next aspect to be taken into account is the German drug law. This states that everybody, who does store a drug in order to offer or provide, or does actually provide or offer a drug, which has not been registered but falls under the rules of registration according to the German drug law, does perform a condemnable action.

Hence some sectors of the legislation might force doctor to prescribe "Off-Label" and another sector might force him not to do so and there is no consistent jurisdiction.

After all the relevant sectors of the German legislation (incl. the most relevant law suites) and their impact on the "Off-Label" use of medicinal products have been discussed some possible solutions are presented.

In its reasons for judgment the federal social court states on at least one occasion that the gap in the German drug law is the origin of the "Off-Label" problem.

The most feasible solution would actually contain two steps. The first step would be to include a clear definition of "Off-Label-Use" in the German drug law. The second step would, consequently to the abovementioned, contain the implementation of some changes within the German drug law.

These changes might comprise the implementation and regulation of a special, temporary registration for "Off-Label-Use", which might be mainly based on previous publications and pre-clinical data.

This registration might be limited to a certain timeframe, in which the pharmaceutical company would need to submit a full application.

It might be worth to consider if both, the temporary registration and the full registration, would be associated with some kind of incentives, so it becomes worthwhile for the pharmaceutical company to submit such registrations.

The temporary registration could be granted by a special expert group called "Off-Label", which has already been implemented at the "Bundesinstitut für Arzneimittel und Medizinprodukte" BfArM.

Number of Pages: 48