Clive Brading, Injectables Quality Head at Sanofi, spoke about retrofitting RABS to existing aseptic filling lines at the 24th Annual ISPE Aseptic Processing Technology Conference in Baltimore, MD.

Brading provided practical examples regarding Sanofi’s experience in retrofitting restricted access barrier systems (RABS) to existing sterile product filling lines. He offered some “dos and don’ts” for a successful transition to barrier systems and posited scenarios for when RABS was not the best solution.

“How can the industry adapt existing equipment to include effective barrier systems without going to full isolator technology?” asked Brading. “No one would argue that taking steps to separate the operator, as a main potential source of microbiological contamination, from the exposed product, is an effective way to ensure a more robust process and product quality.”

While he explained the most effective way of doing this is through complete isolation, Brading stated that the use of other barrier approaches can be equally effective, particularly as an alternative to conventional aseptic filling practices.

Brading continued by saying there were a number of reasons for wanting to retrofit RABS: implementation is speedier and more cost effective.

Central to Sanofi’s strategy, he explained to the audience, was ensuring an effective barrier was in place between the operator and the filling process. “Today, Sanofi has more than 100 aseptic filling lines operating in conventional class A / B configuration, located in North and South America, Europe, Russia, India and China.”

New lines required a different approach and Sanofi decided to use full isolator technology. While the initial investment is comparatively higher, long-term costs are lower: the line can be operated in a lower classification area and with less monitoring.

For existing lines, Sanofi chose to have a single solution: an open and active RABS system.  Brading said a closed system was not an option; it is so close to an isolator that moving to isolation would be preferable to RABS, especially in the handling of potent compounds.

He said that both short- and long-sleeve gloves may be used during the process, adding they are a key component of the RABS solution.

Brading then reviewed the concerns Sanofi had before a retrofit of RABS for existing lines: does the line have a good history of operation; do the environmental monitoring results and trends show good performance on the line; are the media fill results always satisfactory; are there technical issues with the line?

He concluded by describing Sanofi’s three-step response:

  1. Conduct a detailed technical evaluation of the line and the feasibility of carrying out operations on the line using gloves ports, with use of 3D CAD to help study activities carried out both in line set up and also in routine filling.
  2. Review the surrounding class B area in which the line is located and ensure good access around the filling line.
  3. Carry out a mock exercise to verify that the retrofit solution functions and allows operation of the line with the doors closed.

“As with all projects, caution is needed. Carried out correctly, we do see this as a possibility to further improve the performance of conventional aseptic filling in a manner which is relatively rapid and cost effective.”