Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective

Abstract

Pharmacogenetics, one of the cornerstones of personalized medicine, has the potential to change the way in which health care is offered by stratifying patients into various pretreatment categories, such as likely responders, likely non-responders or likely to experience adverse drug reactions. In order to advance drug development and regulatory science, regulatory agencies globally have promulgated guidelines on pharmacogenetics for nearly a decade. The aim of this article is to provide an overview of new guidelines for the implementation of pharmacogenetics in drug development from a multiregional regulatory perspective - encompassing Europe, the United States and Japan - with an emphasis on clinical pharmacokinetics.

Characteristics of pharmacogenomics/biomarker-guided clinical trials for regulatory approval of anti-cancer drugs in Japan

“…5 Furthermore, in recent years, draft guidelines focusing on methodological issues using PGx/BM in clinical trials (such as patient selection and enrichment strategy) have been published independently by the European Medicines Agency and US Food and Drug Administration 22,23 All regulatory agencies (European Medicines Agency, Food and Drug Administration and Pharmaceuticals and Medical Devices Agency) in the international conferences on harmonization (ICH) recognize the importance of PGx/BM in clinical trials and encourage the application of PGx/BM in drug development. 2 For promoting the appropriate application of PGx/BM in clinical trials in the era of globalization, establishment of an international guideline would be important. Thus, regulatory collaborations should be further reinforced.…”

“…1 Accordingly, in recent years, PGx/BM has been recognized worldwide as an important tool for drug development and it has also been implemented in regulatory reviews. 2 In oncology, the use of PGx/BM has not only helped in elucidating the underlying molecular mechanism of tumor formation 3 but also contributed to major advances in personalized medicine as novel anti-cancer drugs targeting relevant molecules were successfully developed. 4 As a result, over the last decade more drugs carry PGx/ BM information on their labels (prescribing information in Japan).…”

Promise of Pharmacogenomics for Drug Discovery, Treatment and Prevention of Parkinson's Disease. A Perspective

“…In fact, GWAS for drug response has yielded astounding results (reviewed in [7,8,31]). Unlike standard GWAS, which often require sample sizes in tens of thousands (because the effects sizes of genetic association with disease risk are very small, i.e., odds ratios, OR<1.3), GWAS for drug response have often succeeded with fewer than 100 patients because the genetic associations with drug response are turning out to be very strong.…”

“…The US Food and Drug Administration (FDA), The European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) have been promoting the application of PGx in drug development for a decade [8]. NIH, the major medical research funding agency in the United States and the home for the National Center for Advancing Translational Science, considers PGx essential in translational science and a cornerstone of personalized medicine [9].…”

Systems-Based Approach to Drug Response

“…This type of diagnostic test is commonly known as a ''companion diagnostic.'' To advance new drug development and regulatory science, regulatory agencies globally have promulgated guidelines on PGx for nearly a decade in Europe, the USA, and Japan [7].…”