Masterstudiengang "Drug Regulatory Affairs"


Changes in the Field of Pharmacovigilance within the Scope of the 12th amendment and the drafted 14th amendment of the German Drug Law and the related EU legislation ***

Stefanie Lemke (Abschlußjahr: 2005)


The rapid development in science and globalisation has led to an increase of medicinal products on the market. While this is a positive development for patients on the one hand, it also poses more risks of drug hazards for patients on the other hand. The purpose of Pharmacovigilance is to detect, assess, understand and prevent adverse effects or any other possible drug-related problems.

Pharmacovigilance is governed by regulations of the European Union, which are either directly binding or have to be transposed into national legislation within a given timeframe, and by national legislation.

The purpose of this thesis is to describe the changes, which have been introduced into the 12th amendment of the German Drug Law in the field of pharmacovigilance as a result of the transposition of EU regulation and for other reasons such as the experience made with the old law. The EU regulations include Directive 2001/83/EG (relating to medicinal products for human use), Directive 2001/82/EG (relating to veterinary medicinal products), Directive 2001/20/EG (relating to Good Clinical Practice) and Directive 2002/98/EG (setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components). Besides changes in the field of clinical studies, the changes related to pharmacovigilance belong to the major changes, which were introduced into the 12th amendment of the German Drug Law. In addition, this thesis describes the changes in the field of pharmacovigilance in the drafted 14th amendment of the German Drug Law, in which Directive 2004/27/EC and directive 2004/28/EC (review of pharmaceutical legislation in 2004), will be transposed into national law. The 12th amendment of the German Drug Law came into force on 6 August 2004, while the 14th amendment of the German Drug Law has been planed to come into force latest by 30 October 2005, which is the date set out by the EU regulations.

One of the major changes to pharmacovigilance is the implementation of a central database for the collection and management of pharmacovigilance data, based at EMEA, which has also led to the amendment of the obligations for reporting adverse drug reactions.

Another major change has been the introduction of a new section, section 63b, under chapter 10 „Observation, Collection and Evaluation of Drug Hazards“ of the German Drug Law. The obligations for recording and reporting adverse drug reactions are now arranged under this section and have been deleted from section 29 AMG.

A further major change which was introduced to the 12th amendment of the German Drug Law was the revision of the regulations governing clinical studies and adaptation to the contents of the GCP Directive 2001/20/EC. For the first time, a separate regulation has been issued in Germany with detailed regulations for the conduct of clinical trials. This regulation, which is called “Verordnung über die Anwendung der Guten Klinischen Praxis bei der Durchführung von klinischen Prüfungen mit Arzneimitteln zur Anwendung am Menschen” (GCP-Verordnung - GCP-V) also contains detailed regulations concerning the obligations of the investigator, the sponsor and the competent higher federal authority to report adverse drug reactions which have occurred during a clinical trial.

A further change in the Drug Law is the addition of a law by which the competent higher federal authorities are authorised to levy charges for activities carried out relating to pharmacovigilance.

Furthermore, the submission of PSURs was introduced into the German Drug Law within its 12th amendment, with a maximal interval for submission of 5 years. This is proposed to be reduced to 3 years with the 14th amendment of the German Drug Law and will be done in connection to the new provisions for the renewal of marketing authorisations, which are also to be transposed into national law with the 14th amendment of the drug Law. The marketing authorisation will then be renewed after 5 years and once renewed, the marketing authorisation will be valid for an unlimited period, unless the competent higher federal authority asks for an additional five-year renewal on the grounds of preventing a direct or indirect risk of human or animal health. The reduction of the maximum submission interval will ensure a more frequent assessment of the benefit risk balance of a medicinal product because the assessment of the safety of the product during renewal will lapse after the first or second renewal. The reduction of the maximum interval to 3 years should also reduce the risks to public health due to the more frequent assessment.

The legal basis for pharmacovigilance inspections has also been planed to be implemented with the 14th amendment of the German Drug Law.

Even though many of the changes regarding pharmacovigilance in the 12th and 14th amendment of the German Drug Law will probably lead to an improvement in pharmacovigilance and thus in the safe use of medicinal products and were actually overdue, the new regulations will also add to the burden on the pharmaceutical industry in terms of time and expenses because of an increase in bureaucracy. The new regulations result in more efforts in the maintenance of marketing authorisations under drug safety aspects and within the scope of clinical trials.

In addition to putting regulations in place for increasing the quality of pharmacovigilance, there should be more training of health-care professionals and increasing the awareness of the public concerning the pharmacovigilance system.

Pages: 70, Annexes 28

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