Similarities and differences in the oncology drug approval process between FDA and European Union with emphasis on in vitro companion diagnostics.

Drug approval [U.S. Food and Drug Administration (FDA), or market authorization for the European Union's European Medicines Agency (EMA)] is the most significant regulatory milestone for any drug, as drugs can only be marketed after marketing approval by a health authority. This article focuses on the main regulatory aspects of the drug approval process in the European Union (EU) and the United States. Although the procedures, requirements, and timelines for drug approvals are different between the EU and the United States, several global harmonization efforts have been developed during the past few years to have more consistent regulatory procedures/outcomes in different parts of the world. One of the most different procedures/requirements among these regions is co-development, also known as in vitro companion diagnostic. In the United States, it is expected that for a drug that requires an in vitro diagnostic test to select the population to be treated, the companion diagnostic should be already/concomitantly approved by the FDA. In the EU, these requirements are not as stringent as in the United States. However, it is anticipated that in the very near future, legislation changes in the EU will lead to similar requirements for the companion diagnostics for EMA. In summary, although the principles, procedures, and requirements for drug approvals may differ between the United States and EMA, novel efforts to harmonize them are being considered and implemented, thereby leading to simpler global drug development. It is of outmost importance that drug developers understand and appreciate differences in regional regulations. Otherwise, lack of understanding may lead to rejection or delays in drug approvals for useful anticancer agents. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development."

Approval probabilities and regulatory review patterns for anticancer drugs in the European Union.

AIM: This article reviews outcomes of marketing authorization applications for anticancer drugs in the EU and outlines factors and hurdles of impact. METHODS: Procedures for initial approval of anticancer and non-cancer drugs were analyzed and compared to anticancer drug approvals in the USA and Japan for the same period. RESULTS: From 2006 to 2011, the regulatory review of 46 marketing authorization applications resulted in 29 new cancer drug approvals. The overall approval probability (63%) lagged behind the probability for non-cancer drugs (73%). Longer median active review times in line with additional clock-stop and EU Commission decision-making times as well as submission delays contribute to the 7.2 months median time-to-market delay [95% CI 4.7-15.0 months] compared to the USA; Japanese patients had to wait an additional 25.1 months [95% CI 6.2-34.1 months]. CONCLUSION: Marketing authorization applications for anticancer drugs in the EU are associated with modest approval success. Patients in the USA get access to new products earlier, fostered by the more frequent use of expedited review procedures. So far, both procedures were used in the EU for applications claiming a major public health interest, characterized by pivotal clinical trial hazard ratios below 0.70.