Glass transition temperature
The process was the manufacturing of coagulation factor VIII. Factor VIII is an essential blood-clotting protein, as known as the anti-haemophilic factor (AHF).
The start material was frozen cryoprecipitate (CP). This collected in plastic bags each weighing 8-10 kgs. When in storage, the bags were kept in -40°C. When these were needed for processing, these would be taken out from the freezer and the contents put in the vessel containing a buffer. This allowed the solid CP to dissolve in the buffer and make a viscous liquid which would then be processed further.
Negative tare was used to weigh the bag, transfer the contents into the vessel and reweigh the bag to get the contents that went into the vessel.
The annoying thing about this whole process was how unpredictable it was and the chance of one of the bags to split was highly likely. When these bags split, the contents were all over the place. As this is a highly regulated environment and the process is crucial, the contents on the floor had to be cleaned and were a waste. As this was the starting material, whatever was lost resulted in the eventual loss of the final product. This made the CP recovery 89-92%
There had to be a better way to do this.
Necessity is the mother of invention. The best to take stock of the situation is to take a step back. Because there was a belief there was a better way to do this, there was a willingness to try different things.
Root cause analysis led us to the plastic bags being the culprit. Being a controlled environment and a validated process, you can not change the process parameters without resulting in change control which is a time consuming and expensive process.
The focus was on now, how to change the way the bags behaved without changing the bags themselves. This is when the literature review came to rescue.
Plastic as material behaves like brittle materials below a certain temperature and above a certain temperature, it behaves like a rubbery, elastic material.
After understanding the glass transition temperature, it was decided to get the bags out, and instead of starting the transfer process, the bags could be allowed to thaw. The thawing period had to be such that the bags were malleable and the contents still remained frozen. After some optimisation, the duration of 40 minutes was determined.
The result of this study was, the CP recovery went up to 98-99%. The process unpredictability was reduced.
The indirect benefits were, the team could align their break with the 40-minute thawing period. There was less wastage and the cleaning time was saved.
Header image credit: Chris Lawton @ Unsplash