Jeff Price has specialized in Blow-Fill-Seal technology for 28 years. As Principal Engineer at his own firm, Icon Engineering, he designed what became Rommelag’s 434 BFS rotary manufacturing machine. He also previously supervised BFS design, production, manufacture, test, Process Validation and more as VP of Operations and Engineering at Nephron Pharmaceuticals Corp.
When you’re producing a Blow-Fill-Seal (BFS) plastic container from molten resin, and filling it a second later with heat-sensitive vaccine or other sterile liquid, how do you compensate for a spread of 178 degrees Celsius between the resin and the vaccine?
That is the difference between the temperature of molten plastic as it becomes a brand-new BFS container, and the vaccine that is aseptically filled into it.
For example, let’s say the drug product must remain between 2-8 degrees Celsius in order to retain and ensure its potency and efficacy. Yet the resin must be heated up to 180 degrees in order to be extruded by a BFS machine into a tube, known as a parison, that will contain that vaccine.
As an analytical engineer, I’ve been working on this question since 1997. Working with a NASA consultant company that specialized in thermodynamic modeling, we came up with 19 related variables that together determined the heat of the liquid contents that were filled into a BFS container as it was being formed and sealed.
The results of that work were presented at the BFS Operators Association in 1998 in Boston, Massachusetts.
To start with, although the molten resin is heated to 180 degrees Celsius, the resulting container is roughly 110 degrees by the time the liquid content begins flowing into it. Our model showed that the first drop of liquid to enter the container, naturally, experienced the greatest spike in temperature. The second drop had less of a spike, and the third drop still less, and so on, because of various factors that were cooling both the container and the liquid. (Keep in mind, it’s a very rapid operation; the entire BFS filling step takes less than a half-second for a 0.6ml fill.)
The strategy to keep the API cool is to offset the heat of the plastic, so that the liquid contents don’t wind up absorbing all that heat. There are several strategies to do this, some inherent to BFS technology and some particular to molds and container designs.