Blow-Fill-Seal, also spelled as Blow/Fill/Seal, in this article abbreviated as BFS, is an automated manufacturing process by which plastic containers, such as bottles or ampoules are, in a continuous operation, blow-formed, filled, and sealed. It takes place in a sterile, enclosed area inside a machine, without human intervention, and thus can be used to aseptically manufacture sterile pharmaceutical or non-pharamceutical liquid/semiliquid unit-dosage forms. BFS is an advanced aseptic processing technology that is typically used for filling and packaging of certain sterile liquid formulations like liquid ophthalmics, inhalational anesthetics, or lavaging agents, but can also be used for injectables, parenteral medicines, and several other liquid or semiliquid medications, with fill volumes ranging from 0.1...1000 cm³. Compared against traditional glass ampoules, BFS ampoules are inexpensive, lightweight, and shatterproof. History BFS was developed in the early 1960s at Rommelag. In 1963, Gerhard Hansen applied for a patent on the BFS process. Originally, it was used for packaging of non-sterile products, such as non-sterile medical devices, food, and cosmetics. In the early 1970s, Rommelag's Bottelpack system was first used for packing large volume pharmaceutical solutions. By the late 1980s, BFS had been well-established in the packaging industry, especially for packaging pharmaceutical and healthcare products. During the 1980s and 1990s, BFS came into use for the now common small volume unit-dosage forms. Since the early 2000s, BFS has been emerging as the preferred packaging process for parenteral products. BFS process The BFS process functions similarly to conventional extrusion blow molding, and takes place within a BFS machine. First, a plastic polymer resin is heated to >160 °C and compressed to 35 MPa, allowing it to be extruded in tubular form, and be taken over by an open two-part mold to form the container. Then, the mold closes which welds the bottom of the container. Simultaneously, the parison above the mold is cut, or the filling needles are placed in the parison head without the parison being cut (rotary BFS type). Next, a filling mandrel with blowing air function is placed in the neck area that seals the container. Sterile compressed air is then introduced through the filling mandrel to inflate and form the container. In the BFS process for smaller ampoules the compressed air system is avoided by using vacuum forming the container instead. After the BFS container has been formed, the desired liquid is filled into the container through the filling mandrel unit. Then,