Due to the rapid pandemic of the new coronavirus infection, a state of emergency was declared in Japan in April 2020, which had a great impact on people's lives. Under these circumstances, the development of COVID‒19 Vaccine (ChAdOx1‒S［recombinant］) (VaxzevriaTM Intramuscular Injection) was started by Oxford University for the purpose of preventing COVID-19, and then AstraZeneca took over it. That vaccine was approved in the UK in December 2020. In Japan, an application for manufacturing and marketing approval was submitted in February 2021, and granted a Special Approval for Emergency for the indication of “prevention of infectious diseases caused by SARS-CoV-2” for people aged 18 or older in May 2021. For post-marketing safety measures conducted in COVID-19 pandemic, it includes the Early Post-marketing Phase Vigilance (EPPV), General Use Result Study following the priority survey (by the Scientific Research Group of the Ministry of Health, Labour and Welfare) at the initial stage of administration of the COVID-19 vaccination, Specific Use Result Study targeting vaccinated people with the special background, and the periodic submission of data about post-marketing safety information in and outside Japan. This contribution will describe the safety measures conducted by an unconventional method in the post-marketing setting. Especially, in COVID-19 pandemic, conducting EPPV via Medical Representative (MR) as usual is assumed to lead to a risk to increase the threat of infection to the overwhelmed healthcare professionals； therefore, the interactive EPPV avoiding the direct contact with the healthcare professionals was conducted on the basis of discussion with the regulatory authority prior to the approval, and would be introduced here.