Risk Management Plans in the European Union: Nonclinical Aspects

Within the European Union (EU) there is a requirement to submit a risk management plan (RMP) for a proposed new drug at the time of submission of the Marketing Authorisation Application (MAA). An RMP may also be needed for existing products when there is a significant change to the MAA. Although regulatory guidance is available to help frame what nonclinical data need to be discussed in the RMP, there is little information available on what is considered to be appropriate content. However, the presentation and discussion of generated nonclinical data, and whether any of the study findings pose an actual or potential safety concern for human use, forms a vital component of the RMP. To confirm this situation, data from centrally authorized products in the EU show that the majority of those with a published RMP summary contain information concerning nonclinical aspects of development. This article provides information to aid in the decision making of appropriate nonclinical content in the RMP and highlights the most common nonclinical endpoints discussed in published RMP summaries both as Identified or Potential Risks and as Planned Studies to further evaluate the risk.