DNA-2The ‘Draft guideline on key aspects for the use of pharmacogenomic methodologies in the pharmacovigilance evaluation of medicinal products’ (EMA/281371/2013) has been released for public consultation as of 30 January 2014 with a deadline for comments of 30 July 2014.


This guideline addresses the influence of pharmacogenomics on pharmacovigilance activities, including considerations on how to evaluate the pharmacovigilance related issues for medicinal products with pharmacogenomic associations, and how to translate the results of these evaluations to appropriate treatment recommendations in the labelling.


There is large interindividual variability in the response to drug therapy – in terms of both efficacy and safety, mostly due to gene-environmental interactions. Some of the variation is related to inherited or non-inherited characteristics of the genome, i.e. variations or activation/suppression of genome functions. These genomic variations may relate to drug disposition (pharmacokinetics, PK) or drug action (pharmacodynamics, PD) or to individual’s susceptibility. Consequently, there may be subsets of  patients with a different benefit/risk profile. Genomic factors may play a role in the pathogenesis of  both predictable and idiosyncratic adverse drug reactions (ADRs).
At the time of marketing authorisation, information on the safety of a medicinal product is relatively limited due to many factors, such as small numbers of subjects (including genomic sub-populations) in clinical trials, restricted inclusion criteria, and restricted conditions of drug treatment. Furthermore, rare but serious ADRs (e.g. skin or hepatic reactions) may be identified late in the drug development process or may only be evidenced and characterised after authorisation with increased population exposure.
The identification of sub-populations with either increased or decreased sensitivity to medicines due to genomic factors could reduce both the risk of side effects and the risk of lack of efficacy in those sub-populations. Characterization and categorization of individuals based on genotype or phenotype to genomic sub-populations may lead to a significant increase in therapy benefit, decreased risks or both.


The scope of this guideline is to provide a framework and recommendations on how to evaluate the pharmacovigilance related issues associated with pharmacogenomic biomarkers, and how to translate the results of these evaluations to appropriate treatment recommendations in the labelling. This guideline also clarifies particular aspects of pharmacovigilance and risk minimisation measures relevant to medicinal products with pharmacogenomic associations. These should be considered together with the guidance provided by good pharmacovigilance practice.
Genomic issues related to disease risk and disease progression are not discussed in this guideline unless they are directly related to safety concerns and referred to in the risk management plan (RMP).
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