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Over the last year, several end-users have asked for status update of disposables for a wide variety of final filling applications.
The availability of technology in this area has grown rapidly in the last two years. Here we discuss a recent example of a
successful end-to-end deployment of single-use technology in aseptic filling. This case study was first presented by Nigel
Bell, sterile product lead at GlaxoSmithKline (GSK, Barnard Castle, UK) at IBC's Biopharmaceutical Manufacturing & Development
Summit in San Francisco, CA, in December. For this article, Miriam Monge (MM) talked to Nigel Bell (NB) of GSK, along with
Ernie Jenness (EJ), a development engineer at Millipore (Billerica, MA), one of the main vendors who actively collaborated
with GSK throughout this project.
MM: Nigel, in what context did you start evaluating the use of disposable technologies?
NB: GSK operates two aseptic vial and two syringe facilities, both using fixed and mobile stainless steel systems. These filling
systems are not flexible enough to respond to the needs of a fast growing, varied product portfolio. The evaluation of disposables
for final filling had already started at GSK, but the acceleration was precipitated by the need to rapidly fill a large quantity
of vials for the flu pandemic because we did not have sufficient capacity with the existing setup.
MM: I understand that one factor that motivated you to switch to disposables was that cold fill products challenged the integrity
of hard-piped steam-sterilized stainless steel systems.
NB: The thing that puts a lot of strain on the joints in the stainless steel systems is the polytetrafluoroethylene (PTFE) gaskets.
These plastics do not have a cold flow memory and so do not react well when being heated to 121 °C for sterilization purposes,
then to 5 °C for filling. There have been some problems with leakage over the years.
But even though cold fill products provided the greatest risk from the integrity point of view, there were many other reasons
for the need for change. Stainless steel is fine when you are working with one dedicated product, but as we move to filling
multiple biopharmaceutical products, the cleaning and sterilization issues rapidly become unwieldy. As the needs of our facility
were changing and the regulatory qualification requirements for operations were increasing, it was becoming increasingly challenging
to prove that there was no risk of cross contamination.
MM: You talk about the cost and capacity loss through qualification and routine steam-in-place (SIP) as one of the key challenges
when working with traditional systems.
NB: When you carry out this analysis, you rapidly realize that the opportunities to improve efficiency, increase productivity,
and reduce cost are huge. The time required for cleaning and sterilizing stainless steel; the space and money required for
dedicated areas for clean and dirty vessel storage; the downtime required for cleaning, steaming, and product changeover;
the massive energy consumption required to generate thousands of liters of water for injection (WFI) to clean and steam equipment,
and the cost to make the WFI, are all highly time consuming and offer the potential for efficiency improvement.
Another key concern for us with the traditional systems was the complexity of operation and the associated level of grade
A intrusions. With the existing arrangement using restricted access barriers (RABs), the doors between grades A and B would
be open taking out and replacing equipment, and so on.
MM: What was the timeline for resolving these issues and implementing disposables?
NB: The project started in June 2009 and we needed to start filling in September 2009.