Clinical Development and Regulatory Pathways of Monoclonal Antibodies in Japan.

The past two decades have seen rapid globalization in the development and distribution of pharmaceutical products. There has been an increasing demand to make innovative and life-saving medicines accessible to global populations promptly. However, regional regulatory requirements may slow drug development and approvals. Therapeutic monoclonal antibodies (mAbs) are among the fastest-growing therapeutics in oncology, immunology, and other disease areas. It has often been observed that, after a new therapeutic mAb is approved in the US and the EU, it takes several additional years before the mAb is approved in Japan. The delay in approval, or the drug approval lag, is primarily due to the delayed submission of new drug applications in Japan, which in turn is the result of regulatory requirements for ethnicity-specific clinical data. These regulatory requirements have been evolving for the last 20 plus years to accelerate new drug development and approval in Japan. This review is intended to examine the trend in drug approval lag for therapeutic mAbs in Japan between 2005 and 2020, review clinical data submissions used to support Japan New Drug Application (JNDA) approvals of mAbs, and discuss the implications of the regulatory environments in Japan in comparison with the US and the EU.