ABSTRACT
The number and quantities of reference standards (RS) needed for the quality control of drugs are increasing, bringing great pressure to the companies that calibrate and use RS. This manuscript summarized the four generations of RS including physical RS, paper atlas, substitute RS, and electronic databases. The advantages and disadvantages of each generation were summarized. The concept of digital RS (DRS) was proposed based on this, and the definition, advantages, and technical architecture of DRS were summed up. The 10 characteristics of the five aspects of the DRS were discussed including digital, multi-dimensional, big data, cloud computing, internet, internet of things, sharing, multi-terminal, intelligence, and compliance certification. Then, the necessity of the formation and application of DRS in the holistic quality control of drugs in the era of internet plus is discussed.