gms | German Medical Science

Background: With the European legislation for pharmacovigilance a number of new requirements for the monitoring of the safety of medicinal products was introduced. These requirements were transferred into national legislation (Medicinal Products Act, AMG) and need to be applied irrespective of the type of marketing authorization.

Results: Risk management plans (RMPs) as well as periodic safety update reports (PSURs) are legally required documents for medicinal products. Both documents are stand-alone documents which need to be complete in their own rights and which have different regulatory purposes. With each new marketing authorization application, for instance, a risk management plan now needs to be submitted as well. Some parts of the latter document are the same with regard to content as parts of the PSUR. The part about actions taken in the reporting interval for safety reasons, for example, is relevant both in the RMP and PSUR. Due to the modular structure of the documents these parts can be used for both.

Moreover, information and results of imposed and voluntary so-called post authorization safety studies (PASS) need to be included into RMPs as well as PSURs. Cumulative lists of serious adverse drug reactions derived from PASS, for example, are required to be included and assessed in the frame of a PSUR. On the other hand, PASS imposed with the approval of marketing authorization need to be described in the RMP with objectives and study protocol. Results from PASS as well as their possible impact on the benefit-risk assessment need to be included in the PSUR. Additionally, other legal requirements have implications for the aforementioned documents. Referral procedures of medicinal products mainly result in further measurements such as changes of the product information, creation of information and educational material for patients and healthcare professionals or the initiation of PASS as well as post authorization efficacy studies (PAES). All these measurements need to be included and assessed in the PSUR of the concerned medicinal product and the RMP, if necessary. Changes in the risk-benefit assessment of a product that result during the analysis of data for a PSUR will have an impact on the RMP. Vice versa, a review of signals due to requirements in the RMP might yield results which then need to be described and discussed in the PSUR.

Conclusion: Due to the modular structure of RMPs and PSURs their revision is facilitated. However, the interaction of these documents due to input of data and results from PASS, signal detection and constant benefit-risk assessment as well as their timely update remains a permanent challenge for marketing authorization holders.