The EMEA has published concept paper on the development of the guidelines on the use of pharmacodynamic methodologies in the pharmacokinetic evaluation of medicinal products.  In recent years there has been a rapid development regarding our understanding of the genetics behind interindividual differences in drug response. This development encompasses the area of pharmacodynamics where individual variability in genes encoding drug transporters, and drug metabolising enzymes affects the systemic and target organ exposure as as well as the occurrance of adverse drug reactions to pharmacologically active substances.

A reflection paper on the use of pharmacokinetics in the pharmacokinetic evaluation of medicinal products was published by the EMEA in May 2007. Since the drafting of this reflection paper, progress in the field has been considerable. In the light of evolution and broad acceptance of genotyping methods, as well is increased experience in the use of such pharmacognomic methodologies during drug development, it was considered appropriate to update aline this progress in the guidance on the topic.

The fundamental issues to be discussed in a proposed CHMP guideline is how to implement pharmacogenetics affecting PK in drug development, and the pharmacokinetic variability arising from pharmacogenetic differences may best be determined, how to assess clinical relevance of this pharmacokinetic differences and recommendations on how to reflect these data in the labelling.

The main additional topics to be addressed in the proposed guideline as compared to reflection paper are:

• Clarifications regarding how and when to apply genotype during clinical development.
• Data needed for evaluating the clinical relevance of  pharmacogenetic effect on drug exposure as well as the benefits of applying genotyping during clinical use.
• Recommendations regarding pharmacokinetic studies investigating the effect of polymorphisms at transport level.
• Guidance on specific technical aspects to be considered in accessing clinically relevant polymorphism (e.g. impact of different allelic variants).

Timetable for drawing up this guidance is as follows; it is anticipated that the guidance will be available nine months after adoption of this concept paper on purely six months external consultation, before finalisation within six months. External consultation from the pharmaceutical industry and academics and professional networks is welcomed by the EMEA.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

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