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  • Review and discuss the regulatory considerations for pharmacogenomics set forth by the European Medicines Agency (EMA).
  • Review and discuss the regulatory considerations for pharmacogenomics set forth by the US Food and Drug Administration (FDA).
  • Understand how these regulatory agencies have similarities and differences in their rules and application.


It is inherent to any pharmacotherapy that there is no such thing like one drug or combination of drugs that can cure or alleviate symptoms of all patients suffering from the same defined disease. Drug action and safety is dependent on multiple factors inside and outside the human body; therefore, environment, lifestyle, age, organ function, xenobiotic intake, and our genetic makeup determine the efficacy, efficiency, and ultimately safety of a drug therapy in question. At the genetic level, both “global” and “local” variations must be considered; the former involving the karyotype (gender1 and aneuploidy) and the latter involving polymorphisms in single or multiple genes.2,3 Despite the aforementioned genetic variations, additional conditions influencing the genetic contribution to drug action and safety are subsumed as “epigenetic factors.”4,5 In comparison to “global” and “local” genetic factors, the latter is much more difficult to “pinpoint” in terms of drug action and/or safety. One such example is the methylation pattern of CpG islands. In spite of a certain stability also propagated to next generations, the methylation pattern can change under different “internal” and/or “external” conditions relative to the human body, which are, up to now, only poorly understood.6,7 Even more complex is the situation concerning the methylation of CpG sites adjacent to CpG islands (i.e. CpG shores). These regions seem to be able to change their methylation pattern within hours depending on different stimuli,4 and perhaps drug therapies.8,9 The methylation pattern of genomic DNA together with other epigenetic factors and/or noncoding (nc) RNAs (ncRNAs)10 modulates the stability and amount of mRNA,11 thereby altering the abundance of proteins crucial for drug efficacy, efficiency, and safety. Variations in the described genetic factors ultimately determine the interindividual variability and influence or predict the outcome of drug treatments and therefore provide an important framework for “personalized medicine,”12 which is commonly acknowledged to form the foundation for a better matching between the available and future drugs with the individual situation of patients. Personalized medicine will optimally lead to more efficient and safer drug therapies that result in fewer adverse side effects, and allowing better selection of patients and more rational use of drugs. The new perspective of “personalized medicine” created the need for regulatory agencies to integrate the aspect of PGx into their regulatory framework. This section describes a brief history and gives insights into the “work in progress” regarding the implementation of PGx into the regulatory framework of the EMA.

History of PGx at the EMA

Following a workshop held in June 2000 with main stakeholder ...

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