Abstract: OBJECTIVE To effectively implement the “four strictest” and fulfill the drug safety supervision responsibility of local governments, improve “technical maturity” and “management maturity” through digital reform, and build defense line from laboratory to hospital. METHODS Drawing lessons from the “black box” concept of civil aviation, the Zhejiang Medical Products Administration focused on building the “black box” application of intelligent drug safety supervision for the supervision of drug manufacturing and supply. Used the drug production and marketing enterprise’s own information system, install a data warehouse (“black box”) in the enterprise for receiving and storing key data, and automatically collect the key parameters affecting drug quality, such as material management, production process, quality control, product release, etc. RESULTS The application of the “black box” of intelligent drug safety supervision had deepened the digital tentacles of drug supervision into the enterprise production line. The 4 752 drug production and marketing enterprises had been connected, and 29 340 batches of drugs and 76.55 million pieces of data had been collected. CONCLUSION The application realizes full coverage, all day long, full automatic off-site intelligent supervision of drugs. Fully controlled and strict management, full chain supervision, and strict law enforcement in all time and space were implemented. A new online intelligent control mode for drug safety were built that is “Everywhere, Everytime, Non inductive monitoring. Non bothering, Early warning of minor matters, Strict investigation of major events”.