To start, pharmaceutical grade resin is transferred from a bulk storage container into the BFS machine. There, it is fed into a heated extruder. The extruder provides a uniform oval of hot liquid resin sheet, known as the parison, that will eventually be made into the BFS container.
Gravity carries this parison down; around the filling mandrel and to the molding area where it’s eventually formed, filled, sealed, cooled, and taken down the line for further processing.
Meanwhile, in the formulation suite, a jacketed mix tank is used to compound the drug product and hold it at a cold temperature as it’s fed into the BFS machine. If advanced aseptic methodologies are employed, sterilizing filters are used to sterilize the clean drug product at the point of fill into the BFS container.
The BFS machine is equipped with an intermediate hold tank for the liquid drug. This hold tank is referred to as a “buffer tank.” The buffer tank provides a consistently pressurized system that allows for a high precision of drug product fill volume into all BFS containers across the mold.
The filling mandrel is the last stop for the drug product before it is transferred into the BFS container. There are several important things to know about the filling mandril.
First, the mandril is surrounded by a sheet of molten resin that is waiting to be formed into a container by the BFS mold. The high temperature of this liquid resin could impact the drug product being held in the mandrel. To protect the drug product from this heat, the mandrel is cooled with an active loop of cooling fluid.
Second, the filling mandrel is governed by a pressure/time principle to ensure a controlled fill.
As discussed earlier, the buffer tank is responsible for the precise pressure environment. That requires the valves inside the filling mandrel to be equally as precise. In both cases, the pressure and valve timing can be adjusted with a high degree of precision and accuracy to ensure consistent dose fill size.
This all comes together in a beautiful symphony as the BFS mold closes around the resin and filling mandrel. The mold forms the liquid resin into the shape of the container. As the resin touches the mold it rapidly cools, turning the liquid resin into its final solid form.
The filling mandril then delivers the drug product into the BFS container. As the process continues, the top half of the mold hermetically seals the BFS container, creating an integral, sterile pharmaceutical product in a rapid and continuous 4 second process.