Postmarketing Surveillance Studies-An Industry Perspective on Changing Global Requirements and Implications.

PURPOSE This article describes postmarketing surveillance (PMS) study regulations and expectations of the regulatory agencies in 5 countries. With a focus on postapproval drug safety, there is a continuous need for understanding the benefit-risk profile of an approved drug. In addition to spontaneous adverse-event reporting, regulatory agencies seem to be more reliant on PMS studies. The opportunity to systematically monitor use in special populations, such as elderly patients and those with comorbid conditions, also presents itself during postmarketing use. Regulatory agencies in Japan, the Republic of Korea, and Mexico are requiring such studies as standards or conditions of drug approvals and license renewals. These studies are meant to be observational and noninterventional, over specified time periods. Studies are required specifically for following up treated patients in clinical practice, with the main objective of collecting safety data to further characterize the benefit-risk profile that was established during clinical trials and particularly in the country-specific population. METHODS We reviewed and compared the published PMS guidelines and requirements in Japan, the Republic of Korea, the People's Republic of China, India, and Mexico. Interpretations of the guidelines and requirements are included and are based on direct interactions with the different regulatory agencies. FINDINGS We note that the different country PMS guidelines are at varying points in development. While some countries have more comprehensive guidelines, in others, the guidelines are still evolving. The similarities among guidelines include the requirements of the content and format of protocols, periodic reports, and interim reports of PMS studies. The differences in the requirements of PMS studies, such as sample size and study duration, are noticeable. These protocols are to be submitted, together with the respective risk-management plans, for approval by the regulatory authority prior to implementation of the study. IMPLICATIONS Conventional drug discovery and approval processes are well understood, and there are ample regulatory guidelines and International Conference of Harmonisation-based reference documents for understanding the path of the drug-approval process. Limited information is currently available with regard to the regulations and how PMS studies should be developed and evaluated. Some of the country-specific elements included can inform readers while they prepare to develop and implement PMS study protocols.