The development of flexible blood containers in the 1950s enabled collection of blood into containers that were integrally connected. This first iteration of closed systems resulted in marked decrease in danger of contamination of transfusion products. Subsequent developments in these systems included special engineering of cell separators and a sterile connection device also known as a "tubing welder." As transfusion and cell therapy development progressed, so did the approach to closed systems and, in addition to systems that were geometrically closed, there were those known as "functionally closed systems." This progression brought with it confusion related to the scientific and regulatory aspects of closed systems. This session will include a brief historical overview of the subject, perspectives on development of products from scientists in industrial and academic organizations and comments on regulatory aspects.