EMA Guidance on Genetic Variability

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The EMA has published a guideline that addresses the influence of patients? genetic variability on drug pharmacokinetics.

The EMA has published a guideline that addresses the influence of patients’ genetic variability on drug pharmacokinetics. The guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products clarifies the requirements for drug developers to analyse the effect of genetic variability on their medicines. Adopted by the EMA’s Committee for Medicinal Products for Human Use in January following a public consultation, the guideline is expected to come into effect on 1 August 2012.

Genetic variation can affect the body’s absorption, distribution, metabolism and excretion of medicines, which can subsequently impact a medicine’s benefits and risks. Although pharmacogenetics are not equally important for every drug, the guideline recommends that prospective banking of DNA for genotype analyses be conducted in all clinical phases of development. Even if there is no obvious indication of a genetic influence on pharmacokinetics, effects may be identified at later stages of development or in postmarketing, which was the case for tamoxifen and clopidogrel where activation by polymorphic enzymes was identified during pharmacovigilance monitoring.

According to the guidance, studies of the effect of pharmacogeneitcs will usually be required when the magnitude of interindividual variation in drug exposure is high enough to potentially affect a medicine’s safety and/or efficacy. The guideline provides recommendations on where pharmacogenetics should be implemented into the drug development process and applies mainly to small-molecule drugs, as the genetic effects on the pharmacokinetics of biological drugs are not yet as well understood.

The guideline also addresses:


  • recommendations and requirements for study designs, subject selection and sampling
  • how to evaluate the clinical impact of genetic differences between patients and recommendations for further studies
  • possible consequences of differences and the impact on treatment recommendations and labelling
  • consideration of drug–drug interactions

effects of impaired or immature organ functions on pharmacogenetics related pharmacokinetic studies.

The full guideline can be read on the EMA website.